ZFP36

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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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.[1][2] It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.[3]

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.[4] Mice deficient in TTP develop a complex syndrome of inflammatory diseases.[4]

Interactions

ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH,[5] and with NUP214, a member of the nuclear pore complex.[6]

Regulation

Post-transcriptionally, TTP is regulated in several ways.[3] 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.[3] There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.[3]

References

  1. 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. PMID 1699942.
  2. "Entrez Gene: ZFP36 zinc finger protein 36, C3H type, homolog (mouse)".
  3. 3.0 3.1 3.2 3.3 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.
  4. 4.0 4.1 Carballo E, Lai WS, Blackshear PJ (August 1998). "Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin". Science. 281 (5379): 1001–5. doi:10.1126/science.281.5379.1001. PMID 9703499.
  5. 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.
  6. 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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