ZFP36L1 phospho S334
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). 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 (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).
Post-translational modifications
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).
Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203 (PubMed:17030608).
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).
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasmic granule
- Cytoplasm
- P-body
- 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).
Alternative names
BERG36, BRF1, ERF1, RNF162B, TIS11B, ZFP36L1, mRNA decay activator protein ZFP36L1, Butyrate response factor 1, EGF-response factor 1, TPA-induced sequence 11b, ERF-1, ZFP36-like 1