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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 (PubMed:12198173, PubMed:15467755, PubMed:15538381, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25014217, PubMed:25106868, PubMed:26542173). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258). Functions by recruiting the CCR4-NOT deadenylase 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 (PubMed:15687258, PubMed:18326031, PubMed:25106868). Also induces the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:12198173, PubMed:15467755, PubMed:15538381, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25014217, PubMed:25106868, PubMed:26542173). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (By similarity). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress (PubMed:24700863). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (PubMed:20702587). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (PubMed:26542173). 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 (By similarity). May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (PubMed:25014217). 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 (By similarity). 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 (By similarity). Participates in the delivery of target ARE-mRNAs to processing bodies (PBs) (PubMed:17369404). 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 (PubMed:21832157). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in vasculogenesis and endocardial development (By similarity). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (PubMed:27182009). Plays a role in myoblast cell differentiation (By similarity).SUBUNIT Associates with the cytoplasmic CCR4-NOT deadenylase and RNA exosome complexes to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:15687258, PubMed:18326031, PubMed:25106868). Interacts with CNOT1 (PubMed:25106868). Interacts (via N-terminus) with CNOT6 (PubMed:15687258, PubMed:18326031). Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868). Interacts with DCP1A (PubMed:15687258). Interacts (via N-terminus) with DCP2 (PubMed:15687258, PubMed:18326031). Interacts (via N-terminus) with EXOSC2 (PubMed:15687258, PubMed:18326031). Interacts with XRN1 (PubMed:15687258). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (PubMed:15538381, PubMed:17030608, PubMed:18326031). Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity).INTERACTION Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner (By similarity). Component of cytoplasmic stress granules (PubMed:15967811). Localizes in processing bodies (PBs) (PubMed:17369404).TISSUE SPECIFICITY Expressed mainly in the basal epidermal layer, weakly in the suprabasal epidermal layers (PubMed:27182009). Expressed in epidermal keratinocytes (at protein level) (PubMed:27182009). Expressed in osteoblasts (PubMed:15465005).INDUCTION Down-regulated under hypoxic conditions in endothelial cells (at protein level) (PubMed:21832157). Up-regulated by growth factor (TGF-beta), cytokines, tumor necrosis factor (TNF) and epidermal growth factor (EGF) in keratinocytes (PubMed:20166898). Up-regulated also by glucocorticoid dexamethasone in keratinocytes (PubMed:20166898). Up-regulated in keratinocytes in response to wounding in a p38 MAPK-dependent manner (PubMed:20166898, PubMed:27182009). Up-regulated by the parathyroid hormone (PTH) in osteoblast-like cells in a cAMP/PKA-dependent manner (PubMed:15465005, PubMed:19179481). Up-regulated in response to adrenocorticotropic hormone (ACTH) (PubMed:19179481). Up-regulated during monocyte/macrophage differentiation in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (PubMed:26542173). Down-regulated by butyrate in colorectal cancer cells (PubMed:10367403).PTM Phosphorylated (PubMed:19179481). Phosphorylated by RPS6KA1 at Ser-334 upon phorbol 12-myristate 13-acetate (PMA) treatment; this phosphorylation results in dissociation of the CCR4-NOT deadenylase complex and induces p38 MAPK-mediated stabilization of the low-density lipoprotein receptor LDLR mRNA (PubMed:25106868). Phosphorylated by protein kinase AKT1 at Ser-92 and Ser-203 in response to insulin; these phosphorylations stabilize ZFP36L1, increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization (PubMed:15538381, PubMed:17030608). AKT1-mediated phosphorylation at Ser-92 does not impair ARE-containing RNA-binding (PubMed:15538381). Phosphorylated at Ser-54, Ser-92 and Ser-203 by MAPKAPK2; these phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization in a protein kinase AKT1-independent manner (PubMed:18326031). MAPKAPK2-mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE-containing RNA-binding (PubMed:18326031). Phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization during early adipogenesis in a p38 MAPK- and AKT-dependent manner (By similarity).PTM Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203 (PubMed:17030608).
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