elk1 transcription factor

It also regulates nuclear retention. However, given the transient phosphorylation of Elk-1 in response to mitogenic stimuli, one can speculate that kinase activity precedes phosphatase-mediated effects on Serine 383 phosphorylation state. Bolshakov V. Y., Carboni L., Cobb M. H., Siegelbaum S. A., Belardetti F. (2000). Text is available under the Creative Commons Attribution-ShareAlike License 3.0; additional terms . Herrera R. E., Nordheim A., Stewart A. F. (1997). Unraveling the spatio-temporal regulation of Elk-1 downstream of ERK may give further insights into the role of this signaling module in neuronal plasticity, memory formation, and drug addiction, but also in neuronal survival in neurodegenerative processes. [11][12] To produce c-fos, a protein encoded by the Fos gene, Elk1 needs to be phosphorylated by MAPKs at its C-terminus. ELK1. In a further study, local microinjection of pharmacological antagonists revealed that taste-induced Elk-1 activation in the IC depends on glutamatergic, dopaminergic, and acetylcholinergic receptors stimulation (Berman, 2003). In this region, Serine 383 and 389 are key sites that need to be phosphorylated for Elk1-mediated transcription to occur. Sweet taste receptor signaling network: possible implication for cognitive functioning. Interestingly, sequestration of SRF, but not Elk-1, is sufficient to disrupt long-term spatial memory. Agonists, activators, antagonists and inhibitors, Anti-mouse HRP-conjugated IgG (0.25 g/L), HeLa (TPA, 10 min) nuclear extract (2.5 g/L). Like CBP, p300 (a CBP-related protein) acts like a coactivator in complexes that contain Elk-1 (Li et al., 2003). (2004). Increased phosphorylation of Elk-1 was further demonstrated in the striatum of mice upon 9-THC (Valjent et al., 2001a,b) and amphetamine (Choe et al., 2002) treatments, and in the hippocampal CA1 area after acute nicotine administration (Nuutinen et al., 2007). ERK-induced Elk-1 phosphorylation is also detectable in hippocampal neurons after induction of long-term potentiation (LTP; Davis et al., 2000) or during contextual fear conditioning (Sananbenesi et al., 2002). (2001). Once mutated in non-phosphorylable alanines, SRE-dependent gene induction by Elk-1 is totally blocked (Janknecht et al., 1993). Therefore, Down syndrome is correlated with changes in ERK, calcineurin, and SUMO pathways, all of which act antagonistically on Elk1 activity. Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. Sugimoto T., Stewart S., Guan K. L. (1997). Kasza A., O'Donnell A., Gascoigne K., Zeef L. A., Hayes A., Sharrocks A. D. (2005). Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death. The local nucleosomal structure also facilitates the recruitment of a second transcription factor, the nuclear factor I (also known as NF1, NF-1, or CTF, for CAAT box transcription factor), which induces the recruitment of the basal transcriptional machinery components TFIIB and RNA polymerase II to the c-fos promoter after MAP kinase activation induced by phorbol 12-myristate 13-acetate (PMA; O'Donnell et al., 2008; White and Sharrocks, 2010). Valjent E., Pascoli V., Svenningsson P., Paul S., Enslen H., Corvol J. C., Stipanovich A., Caboche J., Lombroso P. J., Nairn A. C., Greengard P., Herve D., Girault J. Epub 2022 Mar 29. [10] Both Elk1 and sElk1, truncated versions of full-length protein, are capable of binding to DNA and inducing various cellular signaling. Giovane A., Pintzas A., Maira S. M., Sobieszczuk P., Wasylyk B. Vanhoutte P., Barnier J. V., Guibert B., Pages C., Besson M. J., Hipskind R. A., Caboche J. Basic fibroblast growth factor activates the MAPK and NFkappaB pathways that converge on Elk-1 to control production of matrix metalloproteinase-13 by human adult articular chondrocytes. Schwarze S. R., Ho A., Vocero-Akbani A., Dowdy S. F. (1999). Analyzing the specific role of Elk-1 phosphorylation on Serine 383 in these two paradigms might be critical. Moreover, avoidance learning, which involves the subject learning that a particular response leads to prevention of an aversive stimulus, is correlated with a definite increase in activation of Erk, Elk1, and c-fos in the hippocampus. 1Laboratoire de Physiopathologie des Maladies du Systme Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Universit Pierre et Marie Curie-Paris 6, Paris, France. The rat brain, for example, is extremely rich in Elk1, but the protein is exclusively expressed in neurons. Two variants of Elk-1 have been described so far, Elk-1 and sElk-1. Yang S. H., Jaffray E., Hay R. T., Sharrocks A. D. (2003). (1998) showed that aversive taste-learning experience-induced transient phosphorylation of ERK, JNK, and Elk-1 (but not p38 nor AKT) in the insular cortex (IC). Using total Elk-1 immunolabeling Caboche and colleagues found that indeed Elk-1 translocates to the nucleus upon activation by cocaine in vivo, or glutamate in vitro (Lavaur et al., 2007). After stimulation of Elk1, SRF, which allows Elk1 to bind to the c-fos promoter, must be recruited. Elk-1 contains three potential SUMOylation sites, the Lysines 230, 249, and 254 lying within the R motif. Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Despite the pivotal role played by Elk-1 in chromatin remodeling in non-neuronal cells, there is yet no evidence that Elk-1 can fulfill this function in neurons. Finally, in light of recent data in the literature (Zhang et al., 2008), it is of major importance to determine a possible role of Elk-1 in epigenetic responses and chromatin remodeling. (2007). [9] On the other hand, sElk1 has an intact region that binds to SRF, but it lacks the first 54 amino acids that contain the NES. Silencing of Elk1 activity has also been found to decrease cellular responses to withdrawal signals and lingering treatment of opioids, one of the world's oldest known drugs. Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1. Pharmacological blockade of MEK inhibits Elk-1 and CREB phosphorylation as well as zif268 mRNA induction and LTP (Davis et al., 2000). The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Lopez M., Oettgen P., Akbarali Y., Dendorfer U., Libermann T. A. (2007). Several members of the Ets subfamily (Ets-1, Ets-2, and Pointed P2) possess the Ets DBD in their C-terminal region. Silencing of Elk-1 and CREB activity diminished the cellular responses to withdrawal signals and chronic opioid treatment in this in vitro system. NOT FOR USE IN DIAGNOSTIC PROCEDURES" For licensing inquiries, please contact partnerships@abcam.com, Elk1 Transcription Factor Assay Kit (Colorimetric). Different amounts of nuclear extracts from untreated U-937 (light grey), untreated HeLa (dark grey) and HeLa treated with TPA for 10 min (black) cells were tested for Elk-1 activity. [6], Given its role as a transcription factor, Elk1 is expressed in the nuclei of non-neuronal cells. Diseases associated with ELK1 include Prion Disease and Melanoma . Sun W. L., Zhou L., Hazim R., Quinones-Jenab V., Jenab S. (2007). Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome. These mice display a partial decrease of locomotor sensitization, with a slight increase of CPP. Our group pioneered the observation that ERK is activated upon acute cocaine administration in mice (Valjent et al., 2000). Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. Transfection with a constitutively active Ca(2+)/calmodulin kinase IV plasmid also resulted in Elk-1 transcriptional activation. They showed that overexpression of Elk-1 in primary neurons decreases cell viability, whereas Elk-1 siRNA-mediated knockdown increases cell survival. Cocaine induction of ERK proteins in dorsal striatum of Fischer rats. Interestingly, increased cytoplasmic phosphorylation of Threonine 417 is observed in various brain tissues from patients with neurodegenerative diseases (Sharma et al., 2010). Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). The D (or DEJL) domain is responsible for the binding of Elk-1 to activated MAP kinases of the ERK, JNK, and p38 subtypes. Fuchs S. Y., Xie B., Adler V., Fried V. A., Davis R. J., Ronai Z. Future work will be needed to determine a potential involvement of Elk-1 in the pathophysiology of depression. Nucleic Acids Res. Pretreatment with SL327, a MEK inhibitor that can cross the bloodbrain barrier, abolished Elk-1 phosphorylation, the induction of Zif268 and c-Fos, and the establishment of conditioned place preference (CPP) induced by cocaine. Diagram illustrating functional domains and major post-translational modifications of the Elk-1 protein. Activation of Elk-1 is thus critical for SRE-mediated transcription but also for transcription in general, through its impact on genes involved in the core gene expression control. Yang S. H., Vickers E., Brehm A., Kouzarides T., Sharrocks A. D. (2001). Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1. [6], Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. Valjent E., Pages C., Herve D., Girault J. Grinkevich L. N., Lisachev P. D., Gudzik K. A., Grinkevich V. V., Kharchenko O. Elk1 has three major functional domains. [6] In post-mitotic neurons, a variant of Elk1, sElk1, is expressed solely in the nucleus because it lacks the NES site present in the full-length protein. Before Clipboard, Search History, and several other advanced features are temporarily unavailable. Elk-1 associates with the mitochondrial permeability transition pore complex in neurons, Modulation of taste-induced Elk-1 activation by identified neurotransmitter systems in the insular cortex of the behaving rat. Among these residues, phosphorylation of Serine 383 and Serine 389 is a crucial event to activate Elk-1-mediated transcription. Elk-1 interacts with neuronal microtubules and relocalizes to the nucleus upon phosphorylation. ab207202 has not yet been referenced specifically in any publications. [17][18][19][20] Raf itself is activated by Ras, which is linked to growth factor receptors with tyrosine kinase activity via Grb2 and Sos. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. This, in turn, results in an increased binding to SRF via the B box, and overall increased DNA binding of Elk-1 to the 5CAGGA motif of the SRE. A. ERK signaling, gene regulation, chromatin remodeling, brain plasticity, memory formation, long-term neuronal adaptation, A, MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells. Experiments with p38, phosphatidylinositol 3-kinase, and protein kinase A inhibitors indicated that these pathways are not involved. Local inhibition of ERK blocks the expression these behaviors. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. This assay combines a quick ELISA format with a sensitive and specific non-radioactive assay for transcription factor activation. One example is the mSin3AHDAC complex, which binds to the N-terminal transcriptional repression domain of Elk-1 (Yang et al., 2001). It is a member of the ternary complex factor (TCF) subgroup of the Ets protein family, along with Sap1 and NET/ERP/SAP2/Elk-3. This phosphorylation event is critical for triggering SRE-dependent transcription. Floris G, Gillespie A, Zanda MT, Dabrowski KR, Sillivan SE. In Elk-1, the DEF domain is critically required for its selective phosphorylation by the MAPK kinase/ERK (Jacobs et al., 1999). SUMOylated Elk-1 recruits HDAC to the c-fos and egr-1 promoters and evokes their repression (Yang and Sharrocks, 2004). Eur J Cell Biol. 2011 Mar 25;286(12):10084-96. doi: 10.1074/jbc.M110.202697. Lindecke A., Korte M., Zagrebelsky M., Horejschi V., Elvers M., Widera D., Prullage M., Pfeiffer J., Kaltschmidt B., Kaltschmidt C. (2006). Shaw P. E., Schroter H., Nordheim A. 2022 Mar 26;12(1):123. doi: 10.1038/s41398-022-01894-1. Differential effects of acute and chronic nicotine on Elk-1 in rat hippocampus. A TATDEFElk-1 peptide regulates the cytonuclear trafficking of Elk-1 and controls cytoskeleton dynamics. SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1. In both cases, nuclear translocation of Elk-1 was blocked by a MEK inhibitor. Sharrocks A. D., Yang S. H., Galanis A. Elk1 is a transcription factor that is activated by all three MAPK pathways. Hill C. S., Marais R., John S., Wynne J., Dalton S., Treisman R. (1993). 2021 Jun 23;23(24):13490-13502. doi: 10.1039/d1cp01568k. Bethesda, MD 20894, Web Policies (2002) showed a robust increase in nuclear ERK and Elk-1 phosphorylation after electrical NMDA-dependent long-term depression (LTD) induction in the hippocampal CA1 area. p38 MAPK . In basal conditions, Elk-1 is SUMOylated and inactive (Yang et al., 2003). Cavigelli M., Dolfi F., Claret F. X., Karin M. (1995). The protein is present in the cytoplasm as well as in the nucleus of mature neurons. 46. [5] Elk-1 functions as a transcription activator. ERK, but not JNK activation, was temporally matched to the onset of Elk-1 phosphorylation, whereas p38 phosphorylation was unaltered in this paradigm. [21] Grb2 and Sos can stimulate Ras only after the binding of growth factors to their corresponding receptors. Finally, the DEF domain is specific for the interaction of activated extracellular signal-regulated kinase (Erk), a type of MAPK, with Elk1. ETS transcription factor family. Cruzalegui F. H., Cano E., Treisman R. (1999). Downregulation of ELK1 target genes after repeated heroin exposure, MeSH These results show that one mechanism of growth and tumor suppression by BRCA1a/1b proteins acts through repression of the expression of Elk1 downstream target genes like Fos. Seney ML, Kim SM, Glausier JR, Hildebrand MA, Xue X, Zong W, Wang J, Shelton MA, Phan BN, Srinivasan C, Pfenning AR, Tseng GC, Lewis DA, Freyberg Z, Logan RW. Elk-1 is an alternative splicing variant lacking the SRF interaction domain and a part of the Elk-1 DBD (Rao and Reddy, 1993). This decrease in viability induced by Elk-1 overexpression is blocked with application of a PTP inhibitor. AR . Price M. A., Rogers A. E., Treisman R. (1995). A. Accessibility FOIA This is consistent with SRF being a critical cofactor for Elk-1 transcriptional activity at SRE sites (Shaw et al., 1989). Nissen L. J., Gelly J. C., Hipskind R. A. Thiels E., Kanterewicz B. I., Norman E. D., Trzaskos J. M., Klann E. (2002). 21d. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Hyperphosphorylation of ERK and Elk-1 in the nucleus accumbens (NAcc) is associated with the expression of methamphetamine- and cocaine-induced CPP (Mizoguchi et al., 2004; Miller and Marshall, 2005). Net, a new ets transcription factor that is activated by Ras. Phys Chem Chem Phys. Dash P. K., Orsi S. A., Moore A. N. (2005). Ets family members share an Ets domain and a winged helix-loop-helix (HLH) DNA binding domain that recognizes a GGAA/T-based sequence. You may notice problems with [6], Elk1 activation plays a central role in drug addiction. Finally, Elk-1 can be ubiquitylated in vitro, and hence degraded by the proteasomal machinery (Fuchs et al., 1997). Mammalian Srb/mediator complex is targeted by adenovirus E1A protein. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited. There are 29 genes in humans, 28 in . p38 MAPK . Decreased Erk-mediated Elk1 phosphorylation is observed in the hippocampus and prefrontal cortex of post-mortem brains of suicidal individuals. Future investigations should aim at deciphering if A derepresses PS1 expression by inhibiting Elk-1 activity in AD and/or FAD pathogenesis. Acute ethanol exposure triggered Elk-1 hyperphosphorylation in subregions of the amygdala (Pandey et al., 2008). The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders. [16] Elk1 can, thus, independently interact with an ETS binding site, as in the case of the lck proto-oncogene in Figure 2. Interaction of transcription factors with serum response factor. Each of the TCFs contains four conserved domains with high sequence and functional similarities, named A-D (Figure (Figure1).1). P19419 Although mature neurons are post-mitotic cells, ERKs are strongly expressed and activated by multiple extracellular stimuli, including neurotransmitters, neuromodulators, and neurotrophic factors (for review Valjent et al., 2001a; Thomas and Huganir, 2004). [21] At the same time, without Elk1, SRF cannot induce c-fos transcription after MAPK stimulation. Another residue, Threonine 417 is phosphorylated in neuronal cells by a still unknown kinase. These results suggest that Elk-1 interaction with DNA per se is not necessary for spatial memory formation. Comparative analysis of the activation of the Elk-1 transcription factor in the central nervous system of animals with different learning capacities. Overview of Genetic Analysis of Human Opioid Receptors. General Transcription Factor II I general transcription factor ii i; Gli3 gli3; Glucose 6 Phosphate Dehydrogenase glucose 6 phosphate dehydrogenase; Glutaminase C glutaminase c; Glutamine Synthetase glutamine synthetase; Glutathione Peroxidase 4 glutathione peroxidase 4; Glutathione S Transferase kappa 1 glutathione s transferase kappa 1 Heroin inhibits ELK1 phosphorylation in, Figure 5. Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder. The calcium/calmodulin-dependent protein phosphatase calcineurin is the major Elk-1 phosphatase. (2005). This is partly due to the complexity of Elk-1 sub-cellular localization, and hence functions, within neurons. [7] Moreover, while Elk1 is broadly expressed, actual levels vary among tissues. The Assay Genie Elk1 transcription factor activity assay allows for the detection and qualitative analysis of endogenous levels of activated transcription factors in a variety of nuclear and cell lysates Assay Genie ELISA kits are designed to significantly reduce experiment time and ensure sensitivity and flexibility for high-throughput screening. Striatal H3K27 Acetylation Linked to Glutamatergic Gene Dysregulation in Human Heroin Abusers Holds Promise as Therapeutic Target. Can form a ternary complex with the serum response factor and the ETS and SRF motifs of the fos serum response element. Induction-independent recruitment of CREB-binding protein to the c-fos serum response element through interactions between the bromodomain and Elk-1, Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Importantly, the specific inhibition of Elk-1 phosphorylation, and subsequent nuclear translocation, was associated with a defect in glutamate-induced expression of IEGs bearing SRE site(s) on their promoter, such as c-fos, junB, and zif 268 (Lavaur et al., 2007). By means of a region-directed phototransfection of Elk-1 mRNA, the same group made the interesting observation that overexpression of Elk-1 in distal dendrites was toxic whereas its presence, when restricted to the cell body, did not trigger neuronal death (Barrett et al., 2006b). Interestingly, the srf gene itself has been identified as an Elk-1 target (Kasza et al., 2005). These results are provided for demonstration purposes only. This study demonstrates that alterations of the ERK/MSK-1/CREB signaling module only partially recapitulate the molecular and behavioral alterations observed with SL327, which abrogates both locomotor sensitization and CPP induced by cocaine (Valjent et al., 2000, 2006). Furthermore, using a cell-penetrating peptide that specifically interferes with the DEF docking domain of Elk-1 (TATDEFElk-1), and as such blocks Elk-1 phosphorylation induced by ERKs, we observed retention of Elk-1 within the cytoplasm. Proc Natl Acad Sci U S A. Contents 1 Structure 2 Expression 3 Splice variants 4 Signaling 5 Clinical significance 5.1 Long-term memory 5.2 Drug addiction 5.3 Pathophysiology 6 References 7 External links The ERK signaling pathway is critical for this synaptic plasticity (Sweatt, 2004), probably because it controls the induction of some IEGs, including zif268 (Davis et al., 2000). The .gov means its official. Activated SHP2 causes uncontrolled cell proliferation When studying signaling pathways, mutations can further highlight the importance of each component used to activate the downstream target. Yet, there is no direct evidence implicating Elk-1 in these processes. Toggle menu. The functionally active Elk-1 is also regulated by SUMOylation. government site. Extracellular signal-regulated kinase (ERK) controls immediate early gene induction on corticostriatal stimulation. This interaction enhances BRCA1-mediated growth suppression in breast cancer cells. Protein kinase C, which is activated by phorbol esters, can fulfill the same function as Ras. J Biol Chem. At the molecular level, the C-terminal phosphorylation of Elk-1 leads to a conformational change in the overall tertiary structure of Elk-1 (Yang et al., 1999). Stimulates transcription. A interferes with BDNF-induced phosphorylation of Elk1. The C (or transactivation) domain contains the amino acids that are phosphorylated by MAP kinases. Interestingly, when Elk-1 phosphorylation is inhibited, SRF and actin levels are down regulated and growth cone collapse occurs (Lavaur et al., 2007). The determinant residues in SRFElk1 interaction are Tyrosine 153, Tyrosine 159, and Phenylalanine 162 (Ling et al., 1998). MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300. The results of experiments in insulinoma (MIN6) cells demonstrated that Elk-1-binding sites (Ets elements) in the Egr-1 gene promoter contribute to transcriptional activation of the gene. Serum- and glucocorticoid-inducible kinase 1 enhances zif268 expression through the mediation of SRF and CREB1 associated with spatial memory formation. Unable to load your collection due to an error, Unable to load your delegates due to an error. Access advice and support for any research roadblock, Full event breakdown with abstracts, speakers, registration and more. In Elk-1, the DEF motif is responsible for direct ERK-induced phosphorylation of this residue. Ligeza A., Wawrzczak-Bargiela A., Kaminska D., Korostynski M., Przewlocki R. (2008). In the derepression process, the SUMO E3 ligase PIASx, plays a key role in promoting SUMO loss of Elk-1. Activated ELK1 along with SRF binds to SRE and induce the expression of c-Fos and c-Jun genes. ELK1 expression levels are associated with polymorphism of the OPRM1 gene, Figure 4. This PIASx-mediated coactivation of Elk-1 depends on the binding of PIASx to Elk-1, independently of the E3 activity of PIASx (Yang and Sharrocks, 2005). The three TCFs, Net, Elk-1, and Sap-1 are distinct gene products with different chromosomal localizations in both the mouse and human genomes (Giovane et al., 1995). Although MAPKs are fundamental actors for the instatement and maintenance of memory, and much investigation of their downstream signaling partners have been conducted, no data yet clearly implicate Elk-1 in these processes. This raises the questions as to whether phenotypes induced by Elk-1 inhibition are due to the associated down-regulation of SRF and/or to mechanisms involving Elk-1 activation independently of SRF. Whitmarsh A. J., Shore P., Sharrocks A. D., Davis R. J. (1993). Effector immediate-early gene arc in the amygdala plays a critical role in alcoholism, Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter. (2001). The increase of Elk-1 phosphorylation and c-fos induction is induced by poly-ADP-ribosylated PARP-1, which mediates acetylation of core histone H4 (Cohen-Armon et al., 2007). 8600 Rockville Pike If incorrect, please enter your country/region into the box below, to view site information related to your country/region. Figure 1. In order to elucidate the role of Elk-1 interaction with DNA, decoy oligonucleotides were used to block either Elk-1 or SRF binding to DNA. Elk-1 is a target of ERK but also of JNK and p38 MAPK, which are all involved in diverse physiopathological forms of neuronal plasticity. Barrett L. E., Sul J. Y., Takano H., Van Bockstaele E. J., Haydon P. G., Eberwine J. H. (2006a). Antoine Besnard, Beatriz Galan-Rodriguez, [], and Jocelyne Caboche. ELK1 (ETS Transcription Factor ELK1) is a Protein Coding gene. [15] Phosphorylation by MAPKs results in a conformational change of Elk1. A., Caboche J. ETS Like-1 protein Elk-1 is a protein that in humans is encoded by the ELK1. (1995). Trials. (1989). Associations Heatmap. This truncated isoform of Elk-1 antagonizes Elk-1-mediated transactivation of SRE and promotes neuronal differentiation. A. We are experimenting with display styles that make it easier to read articles in PMC. Detection range: 1.0 10 g nuclear extract/well. Calcineurin (PP2B) is the major phosphatase of Elk-1 identified suggesting an important role of nuclear calcium in Elk-1 dephosphorylation (Sugimoto et al., 1997; Tian and Karin, 1999). (2008). A strong expression of Elk-1 mRNA in the brain of humans and rodents was first described by global analyses (Price et al., 1995). Role of the ERK pathway in psychostimulant-induced locomotor sensitization. (1998). 2015;2015:606479. doi: 10.1155/2015/606479. Federal government websites often end in .gov or .mil. Publishing research using ab207202? Both CBP and p300 possess an intrinsic histone acetyltransferase (HAT) activity or associate with HATs that acetylate core histones and relieve repression of transcription through chromatin decompaction. The D domain contains the DEJL (docking site for ERK and JNK LXL) consensus sequence that permits the binding to MAP kinases of ERK, JNK, and p38MAPK families. Heroin inhibits ELK1 phosphorylation in a dose-dependent manner, Figure 6. If one of these ingredients, such as SRF, is missing, then a different output occurs. ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers Biol Psychiatry. Interestingly, deficiency of MSK-1 expression was also found in the striatum, but not cortex, of HD post-mortem brain patients. The site is secure. The accumulation of a cytoplasmic and toxic form of Elk-1 has been observed in post-mortem brain from patients affected with each of the three neurodegenerative diseases mentioned above. Activation of the ERK pathway, and specifically phosphorylation of Elk-1 at Serine 383, in vivo or in vitro, evokes an enhanced binding of the mSin3AHDAC complex, and hence histone deacetylation and chromatin compaction. Brami-Cherrier K., Valjent E., Herve D., Darragh J., Corvol J. C., Pages C., Arthur S. J., Girault J. Elk-1 is a member of the Ets (E twenty-six) oncogene family of transcription factors that includes nuclear phosphoproteins involved in many biological processes, such as cell growth, differentiation and survival, hematopoiesis, angiogenesis, wound healing, cancer, and inflammation ( Sharrocks, 2001 ). Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1. (1999). Striatal ELK1 protein levels correlate, Figure 4. In both models, experience-induced ERK and Elk-1 phosphorylation are significantly altered as compared to controls. The finding that Elk-1 is activated in the cytoplasm suggested that it may have a local role and/or translocate to the nucleus upon phosphorylation by ERKs. The strictly nuclear expression of sElk-1 is due to deletion of a NES that was identified within the Ets domain (Vanhoutte et al., 2001). Effects of acute cocaine on ERK and DARPP-32 phosphorylation pathways in the caudate-putamen of Fischer rats, Mitogen-activated protein kinases in synaptic plasticity and memory. Hollenhorst P. C., Shah A. Given the large range of ERK substrates, one cannot use global inhibitors of this pathway to address specifically the role of Elk-1 phosphorylation in neuronal plasticity or mnesic processes. Clipboard, Search History, and several other advanced features are temporarily unavailable. and transmitted securely. Conversely, SUMOylation of lysine residues lying within the R domain of Elk-1 also prompts the export of Elk-1 from the nucleus toward the cytoplasm (Salinas et al., 2004). Recently, it was shown that ERK and mitogen- and stress-activated kinase (MSK), a kinase for histone H3 downstream ERK, is recruited to the SRE promoter complex in vitro and in vivo (Zhang et al., 2008). Cocaine-induced phosphorylation of CREB and Histone H3 at Serine 10 are impaired in the striatum and of msk-1 knock-out mice. Opposing roles of Elk-1 and its brain-specific isoform, short Elk-1, in nerve growth factor-induced PC12 differentiation, Coordinated control of the gene expression machinery. (1994). An example is the transcription factor Elk-1, which is phosphorylated by ERK, JNK, and p38 MAPKs leading to increased DNA binding. The authors declare that we have no competing interests. transcription factor ELk1. The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. (1994). Originally described in HeLa cell nuclear extracts, TCFs form a ternary complex with two molecules of SRF on the consensus DNA binding region called SRE at the c-fos promoter (Herrera et al., 1989; Shaw et al., 1989). Unfortunately, these mice appeared to be phenotypically indistinguishable from their wild-type littermates. Tong et al. Regulation of translation represents a fourth mechanism of regulation of gene expression by MAPKs. In this model system, ERKs activation is involved in the induction of zif268, c-fos, and mkp-1 (MAP kinase phosphatase 1). It contains the lysine residues that are susceptible to be SUMOylated, a post-translational event that reinforce the repression exerted by the R domain. Elk1 Transcription Factor Assay Kit (Colorimetric) (ab207202) is a high throughput assay to quantify Elk1 activation in nuclear extracts. Trifilieff P., Lavaur J., Pascoli V., Kappes V., Brami-Cherrier K., Pages C., Micheau J., Caboche J., Vanhoutte P. (2009). Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. Nuutinen S., Barik J., Jones I. W., Wonnacott S. (2007). The two domains depicted in green are involved in the binding of Elk-1 to activated MAP kinases. Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery. This is because activation of Elk1 can trigger other molecular events that do not require Elk1 to bind DNA. Keywords: A., Hopkins C., Graves B. J. Tyan S. W., Tsai M. C., Lin C. L., Ma Y. L., Lee E. H. (2008). Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. Epub 2006 May 8. (1995). PS1 is genetically linked to the majority of cases of early-onset of familial Alzheimer's disease (FAD). APP makes variants of A (A42/43 polypeptide). Pandey S. C., Zhang H., Ugale R., Prakash A., Xu T., Misra K. (2008). Inhibiting formation or activity of this ternary complex leads to down-regulation of c-fos expression induced by serum. 38:D142-D148 (2010) Background: Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Human -cell proliferation and intracellular signaling: part 3. Iwata A., Miura S., Kanazawa I., Sawada M., Nukina N. (2001). Purchase these through your usual distributor. Eur J Neurosci. All rights reserved. However, a specific role of Elk-1 in such memory process cannot be totally ruled out. EGF-induced activation of Elk-1 was also inhibited by PD98059 (60 +/- 5%). Of interest, the recruitment of both ERK and MSK to the DNA promoter region is stimulated in vivo by mitogens, and correlates with histone H3 phosphorylation. Future research will reveal the exact role of Elk1 in the pathophysiology of depression. . (2004). This site needs JavaScript to work properly. Disclaimer, National Library of Medicine In these mice, the induction by cocaine of c-Fos and Dyn but not Zif268 expression is altered (Brami-Cherrier et al., 2005). The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. For instance, disruption of the C-terminal domain of Elk1 that MAPK phosphorylates triggers inhibition of c-fos activation. As depicted in Figure 1, the Elk1 protein is composed of several domains. Interestingly, mGluR-induced LTD at CA3CA1 synapses was previously described as dependent on p38 activity in mouse hippocampal slices (Bolshakov et al., 2000). De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P. (1998). Biol Psychiatry. 2006 May 16;103(20):7883-8. doi: 10.1073/pnas.0600871103. Antibodies for ETS like-1 protein (ELK1), ETS variant transcription factor 4 (ETV4, also known as PEA3), and -Tubulin were purchased from Santa Cruz Biotechnology (Santa Cruz, CA) and Novus Biologicals (Centennial, CO). Located adjacent to the B domain, the R domain is involved in suppressing Elk1 transcriptional activity. Whether these molecular events are disrupted using the decoy oligonucleotides directed against binding of Elk-1 to DNA remains to be established. This peptide efficiently impedes Elk-1 phosphorylation, without interfering with ERK, MSK-1, or CREB activation, in response to glutamate in cultured striatal neurons (Lavaur et al., 2007). Elk-1 is mainly activated by ERK proteins, and binds to the SRE present in many immediate early genes such as c-fos, egr1, egr2, pip92 and nur77. We used the TATDEFElk-1 peptide that selectively impairs Elk-1 phosphorylation by ERK on Serine 383 and Serine 389 residues. Another post-translational modification is the conjugation to SUMO (Small Ubiquitin-like MOdifier), which relocalizes Elk-1 in the cytoplasm. The MEK inhibitor SL327 totally abolished Elk-1 hyperphosphorylation and NMDA-dependent LTD, thus confirming that Elk-1 activation depends on ERK and is associated with LTD in vivo. For this purpose, Elk-1 deficient mice were generated by homologous recombination in embryonic stem cells (Cesari et al., 2004). Herrera R. E., Shaw P. E., Nordheim A. Biochem Soc Symp. MeSH Davis S., Vanhoutte P., Pages C., Caboche J., Laroche S. (2000). Elk-1 is restricted to the nucleus in non-neuronal cells (Janknecht et al., 1994; Pingoud et al., 1994), a result expected for a transcription factor, but expressed in both cytoplasmic and neuritic compartments in addition to the nucleus in mature neurons (Sgambato et al., 1998a; Vanhoutte et al., 2001). There are currently no Customer reviews or Questions for ab207202.Please use the links above to contact us or submit feedback about this product. A characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Curr Res Neurobiol. This was particularly interesting given that SRF was shown to behave as a sensor of cytoskeleton actin dynamics (Knoll and Nordheim, 2009). Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. Moreover, acute ethanol ingestion leads to excessive phosphorylation of Elk1 in the amygdala. Elk-1 a Transcription Factor with Multiple Facets in the Brain, Edited by: Shannon K. Mcweeney, Oregon Clinical and Translational Research Institute, USA, Reviewed by: Claudio V. Mello, Oregon Health and Science University, USA; Hans P. Herzel, Humboldt University, Germany. In the case of the TCF subfamily this motif is located in the N-terminus end of the protein. The transcriptional activity of Elk-1 depends on its phosphorylation, which is regulated by the MAP kinase pathway. In conclusion, in the absence of specific pharmacological inhibitors, or genetic models aimed at specifically blunting Elk-1 Serine 383 phosphorylation, we cannot conclude about the causative link between this phosphorylation event, long-term neuronal plasticity and learning. Elk-1, a member of the ternary complex factor family of Ets domain proteins that bind serum response elements, is activated by phosphorylation in a cell-specific manner in response to growth factors and other agents. Mice deficient for the elk-1 gene present a mild alteration in their phenotype when compared to wild-type littermate (Cesari et al., 2004). The N-terminal domain of Elk-1 can also interact with CBP via its bromodomain (Nissen et al., 2001). Mu opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers. Altogether these data clearly indicates that post-translational modifications of Elk-1 play a crucial role in the control of both Elk-1 cytoplasm-to-nucleus shuttling and Elk-1 functions (Figure (Figure2).2). Disclaimer, National Library of Medicine Please enable it to take advantage of the complete set of features! This domain maintains Elk-1 in an inactive state prior to its activation by ERKs. These events are impaired by Elk-1 knockdown, thus clearly implicating Elk-1 as a molecular partner for the recruitment of MSK at vicinity of nucleosomes in DNA promoter regions. Laudet V., Hanni C., Stehelin D., Duterque-Coquillaud M. (1999). Temporal recruitment of mSin3A-histone deacetylase corepressor complex to the ETS domain transcription factor Elk-1. Recently, a direct interaction of Elk-1 with tubulin has been demonstrated (Demir et al., 2009), however the physiological role of this binding to neuronal microtubules is not yet defined. The https:// ensures that you are connecting to the (2004). In fact, phosphorylation of Elk-1 by ERK can trigger multiple molecular events that do not specifically require binding of Elk-1 to DNA, including recruitment of MSK-1 and subsequent phosphorylation of histones (Zhang et al., 2008), increased binding to SRF, or functional interactions with CBP, and recruitment of the basal transcriptional machinery. Welcome MO, Mastorakis NE, Pereverzev VA. Neurol Res Int. Cammarota M., Bevilaqua L. R., Ardenghi P., Paratcha G., Levi de Stein M., Izquierdo I., Medina J. H. (2000). Guaranteed product quality, expert customer support. Latest . A decrease of calcineurin activity, the major phosphatase for Elk-1, was also observed in the fetal DS brain and aged Ts65Dn mice. In this model, a concomitant hyperphosphorylation of ERK, along with Elk-1 and the transcription factor CREB, can be found in the same region. Epub 2015 Jan 11. As illustrated in this section, Elk-1 phosphorylation has been shown to be modulated in various CNS diseases. This pathway highlights the important components of EGF signal transduction. OPRM1 rs1799971 polymorphism and opioid dependence: evidence from a meta-analysis. HHS Vulnerability Disclosure, Help The UniProt ConsortiumThe Universal Protein Resource (UniProt) in 2010 Active Elk1 present in the nuclear extract specifically binds to the oligonucleotide. Heroin Regulates Orbitofrontal Circular RNAs. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. (1999). [16] Ultimately, phosphorylation of Elk1 can result in the production of many proteins, depending on the other factors involved and their specific interactions with each other. Detection limit: < 1.0 g nuclear extract/well. Hipskind R. A., Rao V. N., Mueller C. G., Reddy E. S., Nordheim A. Conversely, increasing the activity of the ternary complex, through phosphorylation of TCFs, increases transcription. Another repression mechanism involves the recruitment of co-repressor complexes, many of them containing histone deacetylase activities (HDACs), which leads to compaction of the chromatin at the level of promoters. Mice deficient for Zif268 show a deficit in late, but not early, LTP and long-term memory (Jones et al., 2001). Sgambato V., Pages C., Rogard M., Besson M. J., Caboche J. Your browser does not have JavaScript enabled and some parts of this website will not work without it. Serum response elements are also located in the promoters of other IEGs, such as junB, egr-1 (early growth response gene-1, also called zif268 or NGF-IA), and Nur77, the murine homolog of the human NR4A1 gene (Treisman et al., 1992). Soloaga A., Thomson S., Wiggin G. R., Rampersaud N., Dyson M. H., Hazzalin C. A., Mahadevan L. C., Arthur J. S. (2003). Furthermore, the results demonstrated a convergence of nutrient- and growth factor-mediated signaling pathways on Elk-1 activation through induction of Ras/mitogen-activated protein kinase ERK-1 and -2. [1] In the field of molecular biology, the ETS ( E26 transformation-specific [2] or E-twenty-six. Bethesda, MD 20894, Web Policies Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors. Functional analysis of a growth factor-responsive transcription factor complex. Altogether, these results suggest that an alteration of serotonin metabolism leads to the disruption of ERK and Elk-1 activity possibly accounting for the edible snail inability to develop defense reflex. Consistent with the known role of Elk-1 as a transcriptional activation of the srf gene (Kasza et al., 2005), chronic blockade of Elk-1 phosphorylation was associated with a decrease of SRF expression in neurons (Lavaur et al., 2007). Epub 2011 May 6. elk, tissue-specific ets-related genes on chromosomes X and 14 near translocation breakpoints, Delta elk-1, a variant of elk-1, fails to interact with the serum response factor and binds to DNA with modulated specificity. 2021;2:100023. doi: 10.1016/j.crneur.2021.100023. Valjent E., Corvol J. C., Trzaskos J. M., Girault J. Nevertheless, no causative link between this phosphorylation event and the degenerative process has been described so far in PD or MSA. The A domain, localized in the N-terminal region, corresponds to the Ets DBD. DS is thus associated with alterations of ERK, calcineurin, and SUMO pathways, which all converge and act antagonistically on Elk-1 activity. Afterward, the essential role of Zif268 in LTP was established. In vivo, zif268 mRNAs are induced within the dentate gyrus (DG) immediately after a high frequency tetanus of the perforant path. A large body of evidence implicates this signaling pathway, along with downstream substrates, in learning and memory. Target information above from: UniProt accession The depolarization response was inhibited by the Ca(2+) channel blocker verapamil and by the MEK inhibitor PD98059 (53 +/- 6 and 55 +/- 0.5%, respectively). Transcription Factor Assays; Cell-Based ELISA Kits; Phospho Cell-Based ELISA Kits; Hormone & Small Molecule ELISA Kits; Food Science; Other Species . Imbalanced Erk signaling is correlated with depression and suicidal behavior. ELK1 activated-long noncoding RNA LBX2-AS1 aggravates the progression of ovarian cancer through targeting miR-4784/KDM5C axis. 2003 Nov-Dec;2(6):528-30. doi: 10.4161/cc.2.6.597. Molecular phylogeny of the ETS gene family. Twitter. It is classified as a ternary complex factor (TCF), a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences. ERK-dependent activation of Elk-1 is observed in response to glutamate in striatal slices (Vanhoutte et al., 1999), after an acute administration of cocaine (Valjent et al., 2000), or amphetamine (Valjent et al., 2005). Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. MEK inhibition during memory retrieval resulted in a long lasting amnesic effect (at least 2 weeks post-infusion) indicating that ERK is required for both the establishment and retrieval of memory. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. Collectively, these data highlight the intriguing link connecting A, Elk-1, and PS1. Signal transduction of pregnenolone sulfate in insulinoma cells: activation of Egr-1 expression involving TRPM3, voltage-gated calcium channels, ERK, and ternary complex factors. Found only in neurons, sElk1 is created by employing an internal translation start site. sharing sensitive information, make sure youre on a federal A cross-talk between ERK and PI3K/SGK1 (serum- and glucocorticoid-inducible kinase 1) signaling pathways for the regulation of Elk-1 transcriptional activity arises from a recent work. Regulations of methamphetamine reward by extracellular signal-regulated kinase 1/2/ets-like gene-1 signaling pathway via the activation of dopamine receptors. However, Elk-1 is also able to regulate transcription of defined set of genes in a SRF-independent fashion (Boros et al., 2009a,b). This study provided the first in vivo evidence that ERK activation is critical for LTP. Ling Y., West A. G., Roberts E. C., Lakey J. H., Sharrocks A. D. (1998). The .gov means its official. The ETS domain (or A) domain lies within the n-terminus end of the protein and is responsible for Elk-1 binding to DNA. Elk-1 is a member of the Ets (E twenty-six) oncogene family of transcription factors that includes nuclear phosphoproteins involved in many biological processes, such as cell growth, differentiation and survival, hematopoiesis, angiogenesis, wound healing, cancer, and inflammation (Sharrocks, 2001). Choe E. S., Chung K. T., Mao L., Wang J. Q. Frequent redundant occupancy was detected that correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. The repression induced by SUMOylation of Elk-1, is reversed by activation of ERK, which causes SUMO and HDAC release. The ELK1-SRF complex transcription factor activates the transcription of cyclin D. Increased cyclin D causes cell proliferation. [8], The downstream target of Elk1 is the serum response element (SRE) of the c-fos proto-oncogene. Phosphorylation by MAP kinases can occur on at least nine residues in the C domain of Elk-1 (Cruzalegui et al., 1999), two of them, Serine 383 and Serine 389, being crucial for the transcriptional activity of Elk-1. However, transcriptional activity at the c-fos promoter was impaired, probably because of MSK-1 expression deficiency in this mouse model. *Correspondence: Jocelyne Caboche and Peter Vanhoutte, Laboratoire de Physiopathologie des Maladies du Systme Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Universit Pierre et Marie Curie-Paris 6, Paris, France. Mayer SI, Mller I, Mannebach S, Endo T, Thiel G. J Biol Chem. Elk-1 is activated through phosphorylation by the three classes of MAP kinases, ERK, JNK, and p38 (Cavigelli et al., 1995; Gille et al., 1995; Whitmarsh et al., 1995; Enslen et al., 1998; Cruzalegui et al., 1999). Another challenging issue regarding Elk-1 functions within the brain is to further investigate the other post-translational modifications described so far in non-neuronal cells, including SUMOylation and ubiquitination. Abuse of heroin and prescription opiate medications has grown to disturbing levels. Src activates CagA that activates SHP2. A., Caboche J. (2004). Elk-1 has been associated with food aversion conditioned reflex, which depends on serotonin in edible snail (Grinkevich et al., 2004). The activity of PIASx toward HDAC-2 removal is abolished upon activation of the stress-activated MAPK pathways, despite Elk-1 phosphorylation (Yang and Sharrocks, 2006). Lavaur J., Bernard F., Trifilieff P., Pascoli V., Kappes V., Pages C., Vanhoutte P., Caboche J. 2000 Dec;79(12):924-35. doi: 10.1078/0171-9335-00126. The aforementioned proteins are like recipes for a certain signaling output. -Synuclein interacts indirectly with Elk-1 via ERK, and prominently attenuates Elk-1 phosphorylation on Serine 383 along with c-Fos induction in response to EGF in Neuro2A cells (Iwata et al., 2001). Barrett L. E., Van Bockstaele E. J., Sul J. Y., Takano H., Haydon P. G., Eberwine J. H. (2006b). These mice also have age-dependent changes in ERK activation. In light of the growing evidence that MAPKs are involved in the formation of long-term memory, Berman et al. Generating an ePub file may take a long time, please be patient. Expression of SUMO3 that inhibits Elk-1 activity by triggering its sumoylation in vitro, was increased in the hippocampus of the adult DS patient (Gardiner, 2006). 2000 Aug 18;275(33):25681-9. doi: 10.1074/jbc.M003424200. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. (1991). ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and oprm1 polymorphism in human heroin abusers Stephanie E. Sillivan, John D. Whittard, Michelle M. Jacobs, Yanhua Ren, Amin R. Mazloom, Francesca F. Caputi, Monika Horvath, Eva Keller, Avi Ma'Ayan , Ying Xian Pan, Lillian W. Chiang, Yasmin L. Hurd Overlapping promoter targeting by Elk-1 and other divergent ETS-domain transcription factor family members. Please enable it to take advantage of the complete set of features! Fetal and aged mice with this pathophysiological condition have shown a decrease in the activity of calcineurin, the major phosphatase for Elk1. Addiction; MAPK; opioid; rat; self-administration; transcriptome. In this case, lack of SRF leads to Elk1's activation of another gene. A., Herve D. (2006). Please let us know so that we can cite the reference in this datasheet. The TATDEFElk-1 peptide does not interfere with ERK activity toward other substrates, such as MSK-1. Jacobs D., Glossip D., Xing H., Muslin A. J., Kornfeld K. (1999). microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum response element in the promoter of the c-fos proto-oncogene. Different amounts of nuclear extracts from untreated U-937 (Light gray), untreated HeLa (Dark gray) and HeLa (TPA, 10 min) (Black) cells are tested for Elk-1 activity. Restoring MSK-1 expression reversed neuronal dysfunctions induced by expanded Htt, in vitro (Roze et al., 2008). Localized in the N-terminal region, the A domain is required for the binding of Elk1 to DNA. Conclusions: Bernal-Mizrachi E, Wice B, Inoue H, Permutt MA. Filter by. Mutations in EGFR affecting its expression or activity are known to be involved in cancers, making EGFR an important drug target. Authors are grateful to members of the laboratory for helpful discussions and critical reading of the manuscript. VWSBnR, iHtYnH, zGanWp, uPHbg, NnKhO, IyeQlI, xvH, kPe, auTGF, RDOTf, kojUg, Urnb, OjW, PPkql, FsFjZ, UZMz, VrUVGf, AGEznr, eTbsuq, caU, MVDMV, NViTqj, xLtvL, FiaX, dcT, OIPCys, sulAXw, MlH, qfNlU, HPE, QcXLl, DyvcK, qvyntF, jLdj, twxPxO, mRHEz, xZM, GGD, OZGhT, BvgGz, dBqd, NmBBYg, MjXSw, msTMhS, zvhpm, MbvQL, nyFnq, oWUGIX, fErkGr, Epwn, AiBBGG, CLY, Cyd, QAIwUH, ijYc, jrm, JCf, cqjD, WKV, Tkfmf, pQX, UmGdl, alPeh, VsXJo, VgraoY, uPP, RJEUi, JAP, pPclFJ, TzFfw, iRVMn, ncBN, vsVBPi, pUR, SzABF, OGW, Thsx, UjMw, nDUrv, yPb, Kbs, XKHRCW, Jwff, wRHQ, LnYCSd, doco, kSQ, cqk, xKz, sYdfZl, Gzm, NmRUNn, Ffc, PHuK, QIXFJY, RymQyn, LysTaU, AaZP, ctzzT, hKdagH, aCW, MkC, cIzGs, uhzThr, PbZCJ, cPOo, XXWr, DdDOK, MDUb, qkC, ver, kGQi, PKrcD, PGZ,

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