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:9703499, PubMed:10330172, PubMed:10751406, PubMed:11279239, PubMed:12115244, PubMed:12748283, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:27193233, PubMed:23644599, PubMed:25815583, PubMed:31439631).
Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258, PubMed:23644599).
Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation (PubMed:23644599).
Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:11719186, PubMed:12748283, PubMed:15687258, PubMed:16364915).
Self regulates by destabilizing its own mRNA (PubMed:15187101).
Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:10330172, PubMed:10751406, PubMed:12115244, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:19188452, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:25815583).
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 (PubMed:18367721).
Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (PubMed:21775632).
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 (PubMed:20702587).
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 (PubMed:18367721).
Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs (PubMed:15766526).
May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro (PubMed:16364915).
Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (PubMed:17369404).
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 (PubMed:27182009).
Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (PubMed:26926077).
Biological Process
Biological Process 3'-UTR-mediated mRNA destabilization Source:UniProtKB5 Publications
Biological Process 3'-UTR-mediated mRNA stabilization Source:UniProtKB1 Publication
Biological Process cellular response to epidermal growth factor stimulus Source:UniProtKB1 Publication
Biological Process cellular response to fibroblast growth factor stimulus Source:UniProtKB1 Publication
Biological Process cellular response to glucocorticoid stimulus Source:UniProtKB1 Publication
Biological Process cellular response to granulocyte macrophage colony-stimulating factor stimulus Source:UniProtKB1 Publication
Biological Process cellular response to lipopolysaccharide Source:UniProtKB1 Publication
Biological Process cellular response to tumor necrosis factor Source:UniProtKB1 Publication
Biological Process hematopoietic stem cell differentiation Source:Ensembl
Biological Process MAPK cascade Source:UniProtKB1 Publication
Biological Process miRNA-mediated gene silencing by inhibition of translation Source:UniProtKB
Biological Process mRNA catabolic process Source:UniProtKB2 Publications
Biological Process mRNA transport Source:UniProtKB1 Publication
Biological Process myeloid cell differentiation Source:Ensembl
Biological Process negative regulation of erythrocyte differentiation Source:UniProtKB1 Publication
Biological Process negative regulation of hematopoietic stem cell differentiation Source:Ensembl
Biological Process negative regulation of inflammatory response Source:Ensembl
Biological Process negative regulation of interleukin-2 production Source:UniProtKB
Biological Process negative regulation of polynucleotide adenylyltransferase activity Source:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase II Source:UniProtKB1 Publication
Biological Process negative regulation of viral transcription Source:UniProtKB1 Publication
Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:UniProtKB1 Publication
Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-independent decay Source:UniProtKB1 Publication
Biological Process nuclear-transcribed mRNA poly(A) tail shortening Source:BHF-UCL1 Publication
Biological Process p38MAPK cascade Source:UniProtKB
Biological Process positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA Source:UniProtKB1 Publication
Biological Process positive regulation of fat cell differentiation Source:UniProtKB
Biological Process positive regulation of intracellular mRNA localization Source:UniProtKB1 Publication
Biological Process positive regulation of miRNA-mediated gene silencing Source:UniProtKB1 Publication
Biological Process positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:UniProtKB1 Publication
Biological Process positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source:UniProtKB1 Publication
Biological Process regulation of keratinocyte apoptotic process Source:UniProtKB1 Publication
Biological Process regulation of keratinocyte differentiation Source:UniProtKB1 Publication
Biological Process regulation of keratinocyte proliferation Source:UniProtKB1 Publication
Biological Process regulation of mRNA stability Source:UniProtKB4 Publications
Biological Process regulation of tumor necrosis factor production Source:UniProtKB1 Publication
Biological Process response to starvation Source:UniProtKB1 Publication
Biological Process response to wounding Source:UniProtKB1 Publication
Cellular Location
Nucleus
Cytoplasm
Cytoplasmic granule
Cytoplasm, P-body
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).
Nucleus
Cytoplasm
(Microbial infection) Colocalizes with HTLV-1 TAX in the nucleus and the cytoplasm in a region surrounding the nucleus.
PTM
Phosphorylated. Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner (PubMed:16702957).
Phosphorylated by MAPKAPK2 at Ser-60 and Ser-186; phosphorylation increases its stability and cytoplasmic localization, promotes binding to 14-3-3 adapter proteins and inhibits the recruitment of cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to the mRNA decay machinery, thereby inhibiting ZFP36-induced ARE-containing mRNA deadenylation and decay processes. Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding. Phosphorylated in a MAPKAPK2- and p38 MAPK-dependent manner upon skeletal muscle satellite cell activation; this phosphorylation inhibits ZFP36-mediated mRNA decay activity, and hence stabilizes MYOD1 mRNA (By similarity).
Phosphorylated by MAPK1 upon mitogen stimulation (By similarity).
Phosphorylated at Ser-66 and Ser-93; these phosphorylations increase in a SH3KBP1-dependent manner (PubMed:20221403).
Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner (PubMed:26926077).
Phosphorylation at Ser-60 may participate in the PKM-mediated degradation of ZFP36 in a p38 MAPK-dependent manner (PubMed:26926077).
Dephosphorylated by serine/threonine phosphatase 2A at Ser-186 (By similarity).
Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway (PubMed:26926077).
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