Protein: mRNA decay activator protein ZFP36L1 (Butyrate response factor 1) (TPA-induced sequence 11b) (Zinc finger protein 36, C3H1 type-like 1) (ZFP36-like 1) (P23950)
Organism: Mus musculus (Mouse)
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 a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). Functions by recruiting the CCR4-NOT deadenylating complex and components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (By similarity). Induces also the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Binds to 3'-UTR ARE of numerous mRNAs. Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress. Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (By similarity). Promotes degradation of ARE-containing pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent signaling pathway, and hence attenuates ESC self-renewal and positively regulates mesendoderm differentiation. May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (By similarity). In association with ZFP36L2 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination and functional immune cell formation. Together with ZFP36L2 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA. Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, plays a role in the regulation of nuclear mRNA 3'-end processing; modulates mRNA 3'-end maturation efficiency of the DLL4 mRNA through binding with an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal in endothelial cells (By similarity). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (By similarity). Plays a role in vasculogenesis and endocardial development. Involved in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role in myoblast cell differentiation.
Subcellular location: Nucleus {ECO:0000269|PubMed:11796723}. Cytoplasm {ECO:0000269|PubMed:11796723, ECO:0000269|PubMed:24700863, ECO:0000269|PubMed:24733888}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q07352}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q07352}. Note=Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner (PubMed:11796723). Component of cytoplasmic stress granules (By similarity). Localizes in processing bodies (PBs) (By similarity). {ECO:0000250|UniProtKB:Q07352, ECO:0000269|PubMed:11796723}.
Interaction partners:
- MAP kinase-activated protein kinase 2
- mRNA decay activator protein ZFP36L2
- m7GpppN-mRNA hydrolase
- 5'-3' exoribonuclease 1
- 14-3-3 protein beta/alpha
- RAC-alpha serine/threonine-protein kinase
- ELAV-like protein 1
- Exosome complex component RRP4
- Exosome complex component RRP43
Sequence:
MTTTLVSATIFDLSEVLCKGNKMLNYSTPSAGGCLLDRKAVGTPAGGGFPRRHSVTLPSSKFHQNQLLSSLKGEPAPSLSSRDSRFRDRSFSEGGERLLPTQKQPGSGQVNSSRYKTELCRPFEENGACKYGDKCQFAHGIHELRSLTRHPKYKTELCRTFHTIGFCPYGPRCHFIHNAEERRALAGGRDLSADRPRLQHSFSFAGFPSAAATAAATGLLDSPTSITPPPILSADDLLGSPTLPDGTNNPFAFSSQELASLFAPSMGLPGGGSPTTFLFRPMSESPHMFDSPPSPQDSLSDHEGYLSSSSSSHSGSDSPTLDNSRRLPIFSRLSISDD