ZFP36

Tristetraprolin (TTP), also known as zinc finger protein 36 homolog (ZFP36), is a protein that in humans, mice and rats is encoded by the ZFP36 gene. It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.

ZFP36
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4J8S
Identifiers
Aliases	ZFP36, G0S24, GOS24, NUP475, RNF162A, TIS11, TTP, zfp-36, ZFP36 ring finger protein
External IDs	OMIM: 190700; MGI: 99180; HomoloGene: 2558; GeneCards: ZFP36; OMA:ZFP36 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 39,406,847 bp End 39,409,412 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 A3|7 16.72 cM Start 28,076,209 bp End 28,079,678 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava gastric mucosa left uterine tube trachea saphenous vein cardia nipple gallbladder upper lobe of left lung right lung Top expressed in granulocyte stroma of bone marrow left lobe of liver ascending aorta aortic valve mesenteric lymph nodes jejunum left lung lobe duodenum decidua More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding C-C chemokine binding 14-3-3 protein binding metal ion binding protein binding single-stranded RNA binding mRNA 3'-UTR AU-rich region binding enzyme binding mRNA binding protein kinase binding RNA binding heat shock protein binding RNA polymerase binding mRNA 3'-UTR binding Cellular component cytoplasm cytoplasmic stress granule nucleus RISC-loading complex ribonucleoprotein complex Dcp1-Dcp2 complex exosome (RNase complex) P-body cytosol CCR4-NOT complex Biological process nuclear-transcribed mRNA poly(A) tail shortening positive regulation of nuclear-transcribed mRNA poly(A) tail shortening mRNA catabolic process regulation of tumor necrosis factor production negative regulation of transcription by RNA polymerase II nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay miRNA-mediated gene silencing by inhibition of translation response to starvation 3'-UTR-mediated mRNA stabilization negative regulation of erythrocyte differentiation cellular response to lipopolysaccharide cellular response to tumor necrosis factor positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA regulation of keratinocyte apoptotic process regulation of keratinocyte proliferation positive regulation of fat cell differentiation cellular response to fibroblast growth factor stimulus cellular response to granulocyte macrophage colony-stimulating factor stimulus negative regulation of viral transcription regulation of keratinocyte differentiation response to wounding positive regulation of gene silencing by miRNA regulation of mRNA stability MAPK cascade cellular response to glucocorticoid stimulus cellular response to epidermal growth factor stimulus positive regulation of intracellular mRNA localization p38MAPK cascade nuclear-transcribed mRNA catabolic process, deadenylation-independent decay gene silencing mRNA transport 3'-UTR-mediated mRNA destabilization negative regulation of polynucleotide adenylyltransferase activity transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7538 22695 Ensembl ENSG00000128016 ENSMUSG00000044786 UniProt P26651 P22893 RefSeq (mRNA) NM_003407 NM_011756 RefSeq (protein) NP_003398 NP_035886 Location (UCSC) Chr 19: 39.41 – 39.41 Mb Chr 7: 28.08 – 28.08 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA. Mice deficient in TTP develop a complex syndrome of inflammatory diseases.

Interactions

ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH, and with NUP214, a member of the nuclear pore complex.

Regulation

Post-transcriptionally, TTP is regulated in several ways. The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, interactions with target mRNAs are affected by the phosphorylation state of TTP, as the protein can be posttranslationally modified by a large number of protein kinases. There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.

Further reading

• Blackshear PJ (2003). "Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover". Biochem. Soc. Trans. 30 (Pt 6): 945–52. doi:10.1042/bst0300945. PMID 12440952.
• Carrick DM, Lai WS, Blackshear PJ (2005). "The tandem CCCH zinc finger protein tristetraprolin and its relevance to cytokine mRNA turnover and arthritis". Arthritis Research & Therapy. 6 (6): 248–64. doi:10.1186/ar1441. PMC 1064869. PMID 15535838.
• Taylor GA, Lai WS, Oakey RJ, et al. (1991). "The human TTP protein: sequence, alignment with related proteins, and chromosomal localization of the mouse and human genes". Nucleic Acids Res. 19 (12): 3454. doi:10.1093/nar/19.12.3454. PMC 328350. PMID 2062660.
• Lai WS, Stumpo DJ, Blackshear PJ (1990). "Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich protein". J. Biol. Chem. 265 (27): 16556–63. doi:10.1016/S0021-9258(17)46259-4. PMID 2204625.
• Taylor GA, Thompson MJ, Lai WS, Blackshear PJ (1995). "Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro". J. Biol. Chem. 270 (22): 13341–7. doi:10.1074/jbc.270.22.13341. PMID 7768935.
• Heximer SP, Forsdyke DR (1993). "A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor". DNA Cell Biol. 12 (1): 73–88. doi:10.1089/dna.1993.12.73. PMID 8422274.
• Huebner K, Druck T, LaForgia S, et al. (1993). "Chromosomal localization of four human zinc finger cDNAs". Hum. Genet. 91 (3): 217–22. doi:10.1007/BF00218259. PMID 8478004. S2CID 35926610.
• Lai WS, Carballo E, Thorn JM, et al. (2000). "Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA". J. Biol. Chem. 275 (23): 17827–37. doi:10.1074/jbc.M001696200. PMID 10751406.
• Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. doi:10.1074/jbc.M108417200. hdl:10261/112516. PMID 11748221.
• Lai WS, Kennington EA, Blackshear PJ (2002). "Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs". J. Biol. Chem. 277 (11): 9606–13. doi:10.1074/jbc.M110395200. PMID 11782475.
• Johnson BA, Stehn JR, Yaffe MB, Blackwell TK (2002). "Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms". J. Biol. Chem. 277 (20): 18029–36. doi:10.1074/jbc.M110465200. PMID 11886850.
• Brooks SA, Connolly JE, Diegel RJ, et al. (2002). "Analysis of the function, expression, and subcellular distribution of human tristetraprolin". Arthritis Rheum. 46 (5): 1362–70. doi:10.1002/art.10235. PMID 12115244.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Amann BT, Worthington MT, Berg JM (2003). "A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold with a disklike structure". Biochemistry. 42 (1): 217–21. doi:10.1021/bi026988m. PMID 12515557.
• Yu H, Stasinopoulos S, Leedman P, Medcalf RL (2003). "Inherent instability of plasminogen activator inhibitor type 2 mRNA is regulated by tristetraprolin". J. Biol. Chem. 278 (16): 13912–8. doi:10.1074/jbc.M213027200. PMID 12578825.
• Sawaoka H, Dixon DA, Oates JA, Boutaud O (2003). "Tristetraprolin binds to the 3'-untranslated region of cyclooxygenase-2 mRNA. A polyadenylation variant in a cancer cell line lacks the binding site". J. Biol. Chem. 278 (16): 13928–35. doi:10.1074/jbc.M300016200. PMID 12578839.