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Gene Review

ZFP36  -  ZFP36 ring finger protein

Homo sapiens

Synonyms: G0/G1 switch regulatory protein 24, G0S24, GOS24, Growth factor-inducible nuclear protein NUP475, NUP475, ...
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Disease relevance of ZFP36


Psychiatry related information on ZFP36

  • Three MRI exams showed no correlate for her neurological symptoms except a small petechial cortical hemorrhage in the right parietooccipital gyrus which may account for her TTP-related anxiety disorder [6].
  • Here we describe a case of a woman who developed a sporadic form of TTP-HUS during a treatment with bupropion for smoking cessation, successfully treated with plasma ex-change therapy [7].
  • It was found that TTP was both statistically and clinically more effective in reducing pathology related to PTSD and that this superiority was maintained and, in fact, became more evident by 3-month follow-up [8].

High impact information on ZFP36


Chemical compound and disease context of ZFP36


Biological context of ZFP36

  • Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed [1].
  • The three known mammalian CCCH tandem zinc finger proteins of the tristetraprolin (TTP) class have recently been demonstrated to be mRNA-binding proteins [18].
  • Conversely, these mRNAs are stabilized in TTP-deficient mice, leading to an inflammatory phenotype characterized by overproduction of these cytokines [18].
  • This up-regulation was confirmed by reverse transcriptase-PCR analysis that revealed a rapid and transient induction of TTP mRNA by TGF-beta 1 in HuT78 cells, primary human T cells, and THP-1 macrophage-monocyte cells [19].
  • To delineate the transcriptional regulation of the TTP gene, a 2.7-kb human TTP promoter region (-2682 to +56 bp relative to the transcription initiation site) was isolated [19].

Anatomical context of ZFP36

  • In this communication, we report that butyrate has differential effects on the transcription of the three human TIS11 family members identified so far in T84 and HT-29 human colorectal cancer cell lines [2].
  • ARE-mRNA localization in PBs is mediated by the TTP N- and C-terminal domains and occurs downstream from mRNA polysome release, which in itself is not sufficient for mRNA PB localization [12].
  • We developed a cell-free system in which TTP and its related proteins stimulated the deadenylation of ARE-containing, polyadenylated transcripts [20].
  • Here we report that glucocorticoids induce the synthesis of TTP mRNA and protein in A549 lung epithelial cells and in rat tissues [21].
  • Expression of mutant TTP in fibroblasts confirmed that serine 220 was one of the major, mitogen-stimulated phosphorylation sites on the protein in intact cells [22].

Associations of ZFP36 with chemical compounds

  • Third, TTP can nucleate PB formation on untranslated mRNAs even when other mRNAs are trapped in polysomes by cycloheximide treatment [12].
  • They are also dispersed by inhibitors of translational elongation and share several protein components, including Fas-activated serine/threonine phosphoprotein, XRN1, eIF4E, and tristetraprolin (TTP) [23].
  • The ability of TTP to promote transcript deadenylation required Mg(2+), but not ATP or prior capping of the RNA substrate [20].
  • Dexamethasone treatment leads to a sustained induction of TTP mRNA expression that is abrogated by RU486 [21].
  • Post-transcriptional regulation occurs by modulation of TNF-alpha mRNA stability via the binding of tristetraprolin (TTP) to the adenosine/uridine-rich elements found in the 3'-untranslated region of the TNF-alpha transcript [24].

Physical interactions of ZFP36

  • Here we identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex [25].

Regulatory relationships of ZFP36

  • The most widely characterized TTP-regulated gene is the AU-rich tumor necrosis factor alpha (TNF-alpha) gene [21].

Other interactions of ZFP36


Analytical, diagnostic and therapeutic context of ZFP36


  1. Genetic variations in ZFP36 and their possible relationship to autoimmune diseases. Carrick, D.M., Chulada, P., Donn, R., Fabris, M., McNicholl, J., Whitworth, W., Blackshear, P.J. J. Autoimmun. (2006) [Pubmed]
  2. Differential effects of sodium butyrate on the transcription of the human TIS11 family of early-response genes in colorectal cancer cells. Maclean, K.N., McKay, I.A., Bustin, S.A. Br. J. Biomed. Sci. (1998) [Pubmed]
  3. Identification of a member of the TIS11 early response gene family at the insertion point of a DNA fragment containing a gene for the T-cell receptor beta chain in an acute T-cell leukemia. Ino, T., Yasui, H., Hirano, M., Kurosawa, Y. Oncogene (1995) [Pubmed]
  4. Expression, purification, and biochemical characterization of the antiinflammatory tristetraprolin: a zinc-dependent mRNA binding protein affected by posttranslational modifications. Cao, H. Biochemistry (2004) [Pubmed]
  5. Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-alpha production, in synovial tissues of patients with rheumatoid arthritis. Tsutsumi, A., Suzuki, E., Adachi, Y., Murata, H., Goto, D., Kojo, S., Matsumoto, I., Zhong, L., Nakamura, H., Sumida, T. J. Rheumatol. (2004) [Pubmed]
  6. Thrombocytopenic thrombotic purpura: severe clinic with no CT, minor MRI, but a SPECT correlate. Baron, Y., Bargemann, T., Harten, P., Gutschmidt, H.J. European journal of radiology. (1999) [Pubmed]
  7. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome after bupropion treatment for smoking cessation. Mele, L., Voso, M.T., Fianchi, L., Leone, G., Pagano, L. Blood Coagul. Fibrinolysis (2003) [Pubmed]
  8. The relative efficacy and treatment distress of EMDR and a cognitive-behavior trauma treatment protocol in the amelioration of posttraumatic stress disorder. Devilly, G.J., Spence, S.H. Journal of anxiety disorders. (1999) [Pubmed]
  9. Involvement of microRNA in AU-rich element-mediated mRNA instability. Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.C., Gram, H., Han, J. Cell (2005) [Pubmed]
  10. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. Bell, W.R., Braine, H.G., Ness, P.M., Kickler, T.S. N. Engl. J. Med. (1991) [Pubmed]
  11. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Carballo, E., Lai, W.S., Blackshear, P.J. Science (1998) [Pubmed]
  12. TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements. Franks, T.M., Lykke-Andersen, J. Genes Dev. (2007) [Pubmed]
  13. Expression and purification of recombinant tristetraprolin that can bind to tumor necrosis factor-alpha mRNA and serve as a substrate for mitogen-activated protein kinases. Cao, H., Dzineku, F., Blackshear, P.J. Arch. Biochem. Biophys. (2003) [Pubmed]
  14. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Kojouri, K., Vesely, S.K., George, J.N. Ann. Intern. Med. (2001) [Pubmed]
  15. Rapid enrichment of HeLa transcription factors IIIB and IIIC by using affinity chromatography based on avidin-biotin interactions. Kasher, M.S., Pintel, D., Ward, D.C. Mol. Cell. Biol. (1986) [Pubmed]
  16. Clopidogrel-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in a kidney/pancreas transplant recipient. Chinnakotla, S., Leone, J.P., Fidler, M.E., Hammeke, M.D., Tarantolo, S. Transplantation (2000) [Pubmed]
  17. Decrease in TTP pools mediated by 5-bromo-2'-deoxyuridine exposure in a human glioblastoma cell line. Shewach, D.S., Ellero, J., Mancini, W.R., Ensminger, W.D. Biochem. Pharmacol. (1992) [Pubmed]
  18. Polymorphisms in the genes encoding members of the tristetraprolin family of human tandem CCCH zinc finger proteins. Blackshear, P.J., Phillips, R.S., Vazquez-Matias, J., Mohrenweiser, H. Prog. Nucleic Acid Res. Mol. Biol. (2003) [Pubmed]
  19. Transcriptional regulation of tristetraprolin by transforming growth factor-beta in human T cells. Ogawa, K., Chen, F., Kim, Y.J., Chen, Y. J. Biol. Chem. (2003) [Pubmed]
  20. Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease. Lai, W.S., Kennington, E.A., Blackshear, P.J. Mol. Cell. Biol. (2003) [Pubmed]
  21. Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally regulate tumor necrosis factor alpha inflammatory signaling. Smoak, K., Cidlowski, J.A. Mol. Cell. Biol. (2006) [Pubmed]
  22. Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro. Taylor, G.A., Thompson, M.J., Lai, W.S., Blackshear, P.J. J. Biol. Chem. (1995) [Pubmed]
  23. Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. Kedersha, N., Stoecklin, G., Ayodele, M., Yacono, P., Lykke-Andersen, J., Fitzler, M.J., Scheuner, D., Kaufman, R.J., Golan, D.E., Anderson, P. J. Cell Biol. (2005) [Pubmed]
  24. Tristetraprolin (TTP)-14-3-3 Complex Formation Protects TTP from Dephosphorylation by Protein Phosphatase 2a and Stabilizes Tumor Necrosis Factor-{alpha} mRNA. Sun, L., Stoecklin, G., Van Way, S., Hinkovska-Galcheva, V., Guo, R.F., Anderson, P., Shanley, T.P. J. Biol. Chem. (2007) [Pubmed]
  25. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Fabian, M.R., Frank, F., Rouya, C., Siddiqui, N., Lai, W.S., Karetnikov, A., Blackshear, P.J., Nagar, B., Sonenberg, N. Nat. Struct. Mol. Biol. (2013) [Pubmed]
  26. Inherent instability of plasminogen activator inhibitor type 2 mRNA is regulated by tristetraprolin. Yu, H., Stasinopoulos, S., Leedman, P., Medcalf, R.L. J. Biol. Chem. (2003) [Pubmed]
  27. The role of mRNA turnover in the regulation of tristetraprolin expression: evidence for an extracellular signal-regulated kinase-specific, AU-rich element-dependent, autoregulatory pathway. Brooks, S.A., Connolly, J.E., Rigby, W.F. J. Immunol. (2004) [Pubmed]
  28. Analysis of the function, expression, and subcellular distribution of human tristetraprolin. Brooks, S.A., Connolly, J.E., Diegel, R.J., Fava, R.A., Rigby, W.F. Arthritis Rheum. (2002) [Pubmed]
  29. Identification of the anti-inflammatory protein tristetraprolin as a hyperphosphorylated protein by mass spectrometry and site-directed mutagenesis. Cao, H., Deterding, L.J., Venable, J.D., Kennington, E.A., Yates, J.R., Tomer, K.B., Blackshear, P.J. Biochem. J. (2006) [Pubmed]
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