Protein: mRNA decay activator protein ZFP36 (G0/G1 switch regulatory protein 24) (Growth factor-inducible nuclear protein NUP475) (Tristetraprolin) (Zinc finger protein 36) (Zfp-36) (P26651)
Organism: Homo sapiens (Human)
Function: Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation. Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs. Self regulates by destabilizing its own mRNA. Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA. Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages (By similarity). Also plays a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response. Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia. Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (By similarity). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA. Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA (By similarity). Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs. Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs. May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro. Involved in the delivery of target ARE-mRNAs to processing bodies (PBs). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing (By similarity). Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages (By similarity). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (By similarity). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis. Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells.
Subcellular location: Nucleus {ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:27182009}. Cytoplasm {ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:14766228, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:20221403}. Cytoplasmic granule {ECO:0000269|PubMed:15014438}. Cytoplasm, P-body {ECO:0000269|PubMed:17369404}. Note=Shuttles between nucleus and cytoplasm in a CRM1-dependent manner (By similarity). Localized predominantly in the cytoplasm in a p38 MAPK- and YWHAB-dependent manner (By similarity). Colocalizes with SH3KBP1 and MAP3K4 in the cytoplasm (PubMed:20221403). Component of cytoplasmic stress granules (SGs) (By similarity). Localizes to cytoplasmic stress granules upon energy starvation (PubMed:15014438). Localizes in processing bodies (PBs) (PubMed:17369404). Excluded from stress granules in a phosphorylation MAPKAPK2-dependent manner (By similarity). Shuttles in and out of both cytoplasmic P-body and SGs (By similarity). {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:20221403}.; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14679154}. Cytoplasm {ECO:0000269|PubMed:14679154}. Note=(Microbial infection) Colocalizes with HTLV-1 TAX in the nucleus and the cytoplasm in a region surrounding the nucleus. {ECO:0000269|PubMed:14679154}.
Interaction partners:
- Exosome complex component RRP43
- CCR4-NOT transcription complex subunit 1
- MAP kinase-activated protein kinase 2
- 5'-3' exoribonuclease 1
- Dual specificity protein phosphatase 1
- Protein argonaute-2
- Tumor necrosis factor
- m7GpppN-mRNA hydrolase
- Transportin-1
- 14-3-3 protein beta/alpha
Sequence:
MDLTAIYESLLSLSPDVPVPSDHGGTESSPGWGSSGPWSLSPSDSSPSGVTSRLPGRSTSLVEGRSCGWVPPPPGFAPLAPRLGPELSPSPTSPTATSTTPSRYKTELCRTFSESGRCRYGAKCQFAHGLGELRQANRHPKYKTELCHKFYLQGRCPYGSRCHFIHNPSEDLAAPGHPPVLRQSISFSGLPSGRRTSPPPPGLAGPSLSSSSFSPSSSPPPPGDLPLSPSAFSAAPGTPLARRDPTPVCCPSCRRATPISVWGPLGGLVRTPSVQSLGSDPDEYASSGSSLGGSDSPVFEAGVFAPPQPVAAPRRLPIFNRISVSE