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Gene Review

ELAVL1  -  ELAV like RNA binding protein 1

Homo sapiens

Synonyms: ELAV-like protein 1, ELAV1, HUR, Hu-antigen R, HuR, ...
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Disease relevance of ELAVL1


High impact information on ELAVL1

  • The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA [4].
  • HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal [5].
  • Consistent with an inhibitory role of Hu proteins in p27 translation, siRNA mediated knockdown of HuR induced endogenous p27 protein levels as well as IRES-mediated reporter translation and leads to cell cycle arrest in G1 [6].
  • The approximately 30-kD ELAV protein HuR specifically bound to RNAs containing an AU-rich element derived from the TNF-alpha mRNA in the in vitro system [7].
  • These data suggest that mammalian ELAV proteins play a role in regulating mRNA stability by influencing the access of degradative enzymes to RNA substrates [7].

Chemical compound and disease context of ELAVL1


Biological context of ELAVL1


Anatomical context of ELAVL1


Associations of ELAVL1 with chemical compounds

  • Here we show that HuR can be methylated on arginine [12].
  • Binding of neuronal ELAV-like proteins to the uridine-rich sequence in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA [16].
  • The present study also showed that the substitutions of glutamic acid at 42 for aspartic acid and leucine at 44 for phenylalanine in the first potent alpha-helix structure of RRM1, as were seen in another ELAV-like protein Hel-N1, markedly affected the RNA binding [17].
  • We have shown that the h1ARE interacts with heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 and the ELAV-like HuR protein [18].
  • The inhibition of CRM1 by leptomycin B leads to the nuclear retention of pp32 and APRIL, their increased association with HuR, and an increase in HuR's association with nuclear poly(A)+ RNA [19].
  • Treatment with the MAP kinase activator, anisomycin, which commonly stabilizes ARE-containing mRNAs, caused rapid nuclear to cytoplasmic shuttling of HuR [20].

Physical interactions of ELAVL1


Co-localisations of ELAVL1

  • Double-labeling immunofluorescence showed that VEGF protein colocalizes with HuR in discrete nuclear compartments and nuclear VEGF protein was increased in hypoxia [25].
  • Here we show that heat shock induces increased association of HuR with pp32 and APRIL through protein-protein interactions and that these ligands partially colocalize with HuR in cytoplasmic foci [26].

Enzymatic interactions of ELAVL1

  • Our findings suggest that Cdk1 phosphorylates HuR during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence [27].

Regulatory relationships of ELAVL1


Other interactions of ELAVL1

  • Influence of the RNA-binding protein HuR in pVHL-regulated p53 expression in renal carcinoma cells [33].
  • In keeping with earlier reports, the elevated cytoplasmic HuR in VHL(+) cells was likely due to the reduced AMP-activated kinase activity in these cells [33].
  • HuR methylation increased in cells that overexpressed CARM1 [12].
  • However, HuR is not a substrate for PRMT1, the most prominent protein-arginine methyltransferase in mammalian cells, which methylates a number of heterogeneous nuclear ribonucleoproteins [12].
  • Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma [23].

Analytical, diagnostic and therapeutic context of ELAVL1


  1. Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. Dixon, D.A., Tolley, N.D., King, P.H., Nabors, L.B., McIntyre, T.M., Zimmerman, G.A., Prescott, S.M. J. Clin. Invest. (2001) [Pubmed]
  2. HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs. Nabors, L.B., Gillespie, G.Y., Harkins, L., King, P.H. Cancer Res. (2001) [Pubmed]
  3. Role of elongin-binding domain of von Hippel Lindau gene product on HuR-mediated VPF/VEGF mRNA stability in renal cell carcinoma. Datta, K., Mondal, S., Sinha, S., Li, J., Wang, E., Knebelmann, B., Karumanchi, S.A., Mukhopadhyay, D. Oncogene (2005) [Pubmed]
  4. Relief of microRNA-mediated translational repression in human cells subjected to stress. Bhattacharyya, S.N., Habermacher, R., Martine, U., Closs, E.I., Filipowicz, W. Cell (2006) [Pubmed]
  5. HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Szabo, A., Dalmau, J., Manley, G., Rosenfeld, M., Wong, E., Henson, J., Posner, J.B., Furneaux, H.M. Cell (1991) [Pubmed]
  6. ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5'UTR. Kullmann, M., Göpfert, U., Siewe, B., Hengst, L. Genes Dev. (2002) [Pubmed]
  7. ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system. Ford, L.P., Watson, J., Keene, J.D., Wilusz, J. Genes Dev. (1999) [Pubmed]
  8. Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma. Erkinheimo, T.L., Lassus, H., Sivula, A., Sengupta, S., Furneaux, H., Hla, T., Haglund, C., Butzow, R., Ristimäki, A. Cancer Res. (2003) [Pubmed]
  9. Tumor necrosis factor alpha induces angiogenic factor up-regulation in malignant glioma cells: a role for RNA stabilization and HuR. Nabors, L.B., Suswam, E., Huang, Y., Yang, X., Johnson, M.J., King, P.H. Cancer Res. (2003) [Pubmed]
  10. The role of human antigen R, an RNA-binding protein, in mediating the stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel mechanism involved in vascular inflammation. Lin, F.Y., Chen, Y.H., Lin, Y.W., Tsai, J.S., Chen, J.W., Wang, H.J., Chen, Y.L., Li, C.Y., Lin, S.J. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  11. HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression. Adams, D.J., Beveridge, D.J., van der Weyden, L., Mangs, H., Leedman, P.J., Morris, B.J. J. Biol. Chem. (2003) [Pubmed]
  12. Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase. Li, H., Park, S., Kilburn, B., Jelinek, M.A., Henschen-Edman, A., Aswad, D.W., Stallcup, M.R., Laird-Offringa, I.A. J. Biol. Chem. (2002) [Pubmed]
  13. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. Rebane, A., Aab, A., Steitz, J.A. RNA (2004) [Pubmed]
  14. Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2. Denkert, C., Koch, I., von Keyserlingk, N., Noske, A., Niesporek, S., Dietel, M., Weichert, W. Mod. Pathol. (2006) [Pubmed]
  15. RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression. Xu, Y.Z., Di Marco, S., Gallouzi, I., Rola-Pleszczynski, M., Radzioch, D. Mol. Cell. Biol. (2005) [Pubmed]
  16. Binding of neuronal ELAV-like proteins to the uridine-rich sequence in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA. Sakai, K., Kitagawa, Y., Hirose, G. FEBS Lett. (1999) [Pubmed]
  17. Analysis of the RNA recognition motifs of human neuronal ELAV-like proteins in binding to a cytokine mRNA. Sakai, K., Kitagawa, Y., Hirose, G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  18. Heterogeneous nuclear ribonucleoprotein C binds exclusively to the functionally important UUUUU-motifs in the human papillomavirus type-1 AU-rich inhibitory element. Sokolowski, M., Schwartz, S. Virus Res. (2001) [Pubmed]
  19. Protein ligands to HuR modulate its interaction with target mRNAs in vivo. Brennan, C.M., Gallouzi, I.E., Steitz, J.A. J. Cell Biol. (2000) [Pubmed]
  20. FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1. David, P.S., Tanveer, R., Port, J.D. RNA (2007) [Pubmed]
  21. Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3'-untranslated region of the androgen receptor messenger RNA. Yeap, B.B., Voon, D.C., Vivian, J.P., McCulloch, R.K., Thomson, A.M., Giles, K.M., Czyzyk-Krzeska, M.F., Furneaux, H., Wilce, M.C., Wilce, J.A., Leedman, P.J. J. Biol. Chem. (2002) [Pubmed]
  22. IL-1beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via the 3' untranslated region: Involvement of divergent RNA-binding factors HuR, KSRP and TIAR. Suswam, E.A., Nabors, L.B., Huang, Y., Yang, X., King, P.H. Int. J. Cancer (2005) [Pubmed]
  23. Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma. Denkert, C., Weichert, W., Winzer, K.J., Müller, B.M., Noske, A., Niesporek, S., Kristiansen, G., Guski, H., Dietel, M., Hauptmann, S. Clin. Cancer Res. (2004) [Pubmed]
  24. Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2. Doller, A., Huwiler, A., Müller, R., Radeke, H.H., Pfeilschifter, J., Eberhardt, W. Mol. Biol. Cell (2007) [Pubmed]
  25. New horizons for VEGF. Is there a role for nuclear localization? Lejbkowicz, F., Goldberg-Cohen, I., Levy, A.P. Acta Histochem. (2005) [Pubmed]
  26. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. Gallouzi, I.E., Brennan, C.M., Steitz, J.A. RNA (2001) [Pubmed]
  27. Nuclear HuR accumulation through phosphorylation by Cdk1. Kim, H.H., Abdelmohsen, K., Lal, A., Pullmann, R., Yang, X., Galban, S., Srikantan, S., Martindale, J.L., Blethrow, J., Shokat, K.M., Gorospe, M. Genes Dev. (2008) [Pubmed]
  28. Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization. Pan, Y.X., Chen, H., Kilberg, M.S. J. Biol. Chem. (2005) [Pubmed]
  29. HuR regulates p21 mRNA stabilization by UV light. Wang, W., Furneaux, H., Cheng, H., Caldwell, M.C., Hutter, D., Liu, Y., Holbrook, N., Gorospe, M. Mol. Cell. Biol. (2000) [Pubmed]
  30. Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2. Tran, H., Maurer, F., Nagamine, Y. Mol. Cell. Biol. (2003) [Pubmed]
  31. Androgens regulate the binding of endogenous HuR to the AU-rich 3'UTRs of HIF-1alpha and EGF mRNA. Sheflin, L.G., Zou, A.P., Spaulding, S.W. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  32. Functional Antagonism Between RNA Binding Proteins HuR and CUGBP2 Determines the Fate of COX-2 mRNA Translation. Sureban, S.M., Murmu, N., Rodriguez, P., May, R., Maheshwari, R., Dieckgraefe, B.K., Houchen, C.W., Anant, S. Gastroenterology (2007) [Pubmed]
  33. Influence of the RNA-binding protein HuR in pVHL-regulated p53 expression in renal carcinoma cells. Galbán, S., Martindale, J.L., Mazan-Mamczarz, K., López de Silanes, I., Fan, J., Wang, W., Decker, J., Gorospe, M. Mol. Cell. Biol. (2003) [Pubmed]
  34. Localization of HuC (ELAVL3) to chromosome 19p13.2 by fluorescence in situ hybridization utilizing a novel tyramide labeling technique. Van Tine, B.A., Knops, J.F., Butler, A., Deloukas, P., Shaw, G.M., King, P.H. Genomics (1998) [Pubmed]
  35. Localization of the human HuR gene to chromosome 19p13.2. Ma, W.J., Furneaux, H. Hum. Genet. (1997) [Pubmed]
  36. Analysis of the 5' end of the mouse Elavl1 (mHuA) gene reveals a transcriptional regulatory element and evidence for conserved genomic organization. King, P.H., Fuller, J.J., Nabors, L.B., Detloff, P.J. Gene (2000) [Pubmed]
  37. Identification of a target RNA motif for RNA-binding protein HuR. López de Silanes, I., Zhan, M., Lal, A., Yang, X., Gorospe, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
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