ZFP36

Description

The ZFP36 (ZFP36 ring finger protein) is a protein-coding gene located on chromosome 19.

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. 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.

ZFP36, also known as Tristetraprolin, is a zinc-finger RNA-binding protein that regulates gene expression by destabilizing mRNA transcripts containing AU-rich elements (AREs) in their 3'-untranslated regions (UTRs). This protein promotes the removal of poly(A) tails from these mRNAs, leading to their degradation and attenuating protein synthesis. ZFP36 acts as a 3'-UTR ARE mRNA-binding adapter protein, communicating signaling events to the mRNA decay machinery. It recruits the deadenylase CNOT7, and likely the CCR4-NOT complex, through association with CNOT1, promoting ARE-mediated mRNA deadenylation. ZFP36 further functions by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs. Notably, ZFP36 self-regulates by destabilizing its own mRNA. It binds to 3'-UTR AREs of numerous mRNAs, including its own, playing crucial roles in diverse cellular processes. ZFP36 contributes to anti-inflammatory responses by suppressing TNF-alpha production through ARE-mediated mRNA decay. It is involved in the regulation of dendritic cell maturation, operating within a negative feedback loop to control the inflammatory response. Moreover, ZFP36 promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A during endothelial cell response to hypoxia. It positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). ZFP36 negatively regulates hematopoietic/erythroid cell differentiation by targeting the transcription factor STAT5B mRNA for decay. It contributes to maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA. Additionally, ZFP36 associates with and regulates the expression of non-ARE-containing target mRNAs, including MHC class I mRNAs. ZFP36 participates in the ARE-mediated mRNA decay mechanism alongside argonaute RISC catalytic components, assisting microRNA (miRNA) targeting of ARE-containing mRNAs. It may also regulate cytoplasmic mRNA decapping, enhancing decapping of ARE-containing RNAs in vitro. ZFP36 is involved in the delivery of target ARE-mRNAs to processing bodies (PBs). Beyond its role in mRNA decay, ZFP36 influences nuclear pre-mRNA processing. It negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages. Furthermore, ZFP36 participates in the regulation of stress granule (SG) and P-body (PB) formation and fusion. ZFP36 plays a role in regulating keratinocyte proliferation, differentiation, and apoptosis. It acts as a tumor suppressor by inhibiting cell proliferation in breast cancer cells.

ZFP36 is also known as G0S24, GOS24, NUP475, RNF162A, TIS11, TTP, zfp-36.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing