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.[5][6] It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.[7]

ZFP36
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesZFP36, G0S24, GOS24, NUP475, RNF162A, TIS11, TTP, zfp-36, ZFP36 ring finger protein
External IDsOMIM: 190700; MGI: 99180; HomoloGene: 2558; GeneCards: ZFP36; OMA:ZFP36 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003407

NM_011756

RefSeq (protein)

NP_003398

NP_035886

Location (UCSC)Chr 19: 39.41 – 39.41 MbChr 7: 28.08 – 28.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[8] Mice deficient in TTP develop a complex syndrome of inflammatory diseases.[8]

Interactions

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ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH,[9] and with NUP214, a member of the nuclear pore complex.[10]

Regulation

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Post-transcriptionally, TTP is regulated in several ways.[7] 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.[7] There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.[7]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128016Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000044786Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ DuBois RN, McLane MW, Ryder K, Lau LF, Nathans D (Dec 1990). "A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence". J Biol Chem. 265 (31): 19185–91. doi:10.1016/S0021-9258(17)30642-7. PMID 1699942.
  6. ^ "Entrez Gene: ZFP36 zinc finger protein 36, C3H type, homolog (mouse)".
  7. ^ a b c d Sanduja S, Blanco FF, Dixon DA (2011). "The roles of TTP and BRF proteins in regulated mRNA decay". Wiley Interdiscip Rev RNA. 2 (1): 42–57. doi:10.1002/wrna.28. PMC 3030256. PMID 21278925.
  8. ^ a b Carballo E, Lai WS, Blackshear PJ (August 1998). "Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin". Science. 281 (5379): 1001–5. Bibcode:1998Sci...281.1001C. doi:10.1126/science.281.5379.1001. PMID 9703499.
  9. ^ Johnson BA, Stehn JR, Yaffe MB, Blackwell TK (May 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.
  10. ^ Carman JA, Nadler SG (March 2004). "Direct association of tristetraprolin with the nucleoporin CAN/Nup214". Biochem. Biophys. Res. Commun. 315 (2): 445–9. doi:10.1016/j.bbrc.2004.01.080. PMID 14766228.

Further reading

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