UniProt functional annotation for P22893



	UniProt functional annotation for P22893

UniProt code: P22893.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Zinc-finger RNA-binding protein that destabilizes numerous 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:10330172, PubMed:10706852, PubMed:10805719, PubMed:15014438, PubMed:15187092, PubMed:15634918, PubMed:17030620, PubMed:19188452, PubMed:20595389, PubMed:21078877, PubMed:22701344, PubMed:27193233). Acts as an 3'- untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:21278420). Recruits deadenylase CNOT7 (and probably the CCR4- NOT complex) via association with CNOT1, and hence promotes ARE- mediated mRNA deadenylation (PubMed:21278420). Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:21278420). Self regulates by destabilizing its own mRNA (PubMed:15187092, PubMed:17288565). Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:11533235, PubMed:15187092, PubMed:16508014, PubMed:17288565, PubMed:17971298, PubMed:20595389, PubMed:21078877, PubMed:21278420, PubMed:22701344, PubMed:27193233). 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 (PubMed:8630730, PubMed:9703499, PubMed:15014438, PubMed:16514065). Plays also 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 (By similarity). Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (By similarity). Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA (PubMed:25815583). Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post- transcriptional level, such as MHC class I mRNAs (By similarity). Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs (By similarity). May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro (By similarity). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing (PubMed:22844456). Negatively regulates nuclear poly(A)- binding protein PABPN1-stimulated polyadenylation activity on ARE- containing pre-mRNA during LPS-stimulated macrophages (PubMed:22844456). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (By similarity). {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10706852, ECO:0000269|PubMed:10805719, ECO:0000269|PubMed:11533235, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15187092, ECO:0000269|PubMed:15634918, ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16514065, ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:17288565, ECO:0000269|PubMed:17971298, ECO:0000269|PubMed:19188452, ECO:0000269|PubMed:20595389, ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:22701344, ECO:0000269|PubMed:22844456, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:27193233, ECO:0000269|PubMed:8630730, ECO:0000269|PubMed:9703499}.

Subunit: Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:20595389, PubMed:21078877). Part of a mRNA decay activation complex at least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes DCP1A and DCP2 (By similarity). Associates with the RNA exosome complex (By similarity). Interacts (via phosphorylated form) with 14-3-3 proteins; these interactions promote exclusion of ZFP36 from cytoplasmic stress granules in response to arsenite treatment in a MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation and decay processes (PubMed:15014438, PubMed:20595389). Interacts with 14-3-3 proteins; these interactions occur in response to rapamycin in an Akt-dependent manner (By similarity). Interacts with AGO2 and AGO4 (By similarity). Interacts (via C-terminus) with CNOT1; this interaction occurs in a RNA-independent manner and induces mRNA deadenylation (PubMed:21278420). Interacts (via N-terminus) with CNOT6 (By similarity). Interacts with CNOT6L (PubMed:21078877). Interacts (via C-terminus) with CNOT7; this interaction occurs in a RNA- independent manner, induces mRNA deadenylation and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389, PubMed:21278420). Interacts (via unphosphorylated form) with CNOT8; this interaction occurs in a RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389). Interacts with DCP1A (By similarity). Interacts (via N-terminus) with DCP2 (By similarity). Interacts with EDC3 (By similarity). Interacts (via N-terminus) with EXOSC2 (By similarity). Interacts with heat shock 70 kDa proteins (By similarity). Interacts with KHSRP; this interaction increases upon cytokine-induced treatment (By similarity). Interacts with MAP3K4; this interaction enhances the association with SH3KBP1/CIN85 (By similarity). Interacts with MAPKAPK2; this interaction occurs upon skeletal muscle satellite cell activation (PubMed:25815583). Interacts with NCL (By similarity). Interacts with NUP214; this interaction increases upon lipopolysaccharide (LPS) stimulation (By similarity). Interacts with PABPC1; this interaction occurs in a RNA-dependent manner (PubMed:20595389, PubMed:21078877). Interacts (via hypophosphorylated form) with PABPN1 (via RRM domain and C-terminal arginine-rich region); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single- stranded poly(A) RNA-oligomer and in a p38 MAPK-dependent-manner and inhibits nuclear poly(A) tail synthesis (PubMed:22844456). Interacts with PAN2 (PubMed:21078877). Interacts (via C3H1-type zinc finger domains) with PKM (By similarity). Interacts (via C3H1-type zinc finger domains) with nuclear RNA poly(A) polymerase (PubMed:22844456). Interacts with PPP2CA; this interaction occurs in LPS-stimulated cells and induces ZFP36 dephosphorylation, and hence may promote ARE- containing mRNAs decay (PubMed:17170118). Interacts (via C-terminus) with PRR5L (via C-terminus); this interaction may accelerate ZFP36- mediated mRNA decay during stress (By similarity). Interacts (via C- terminus) with SFN; this interaction occurs in a phosphorylation- dependent manner (PubMed:11886850). Interacts (via extreme C-terminal region) with SH3KBP1/CIN85 (via SH3 domains); this interaction enhances MAP3K4-induced phosphorylation of ZFP36 at Ser-58 and Ser-85 and does not alter neither ZFP36 binding to ARE-containing transcripts nor TNF- alpha mRNA decay (By similarity). Interacts with XRN1 (By similarity). Interacts (via C-terminus and Ser-178 phosphorylated form) with YWHAB; this interaction occurs in a p38/MAPKAPK2-dependent manner, increases cytoplasmic localization of ZFP36 and protects ZFP36 from Ser-178 dephosphorylation by serine/threonine phosphatase 2A, and hence may be crucial for stabilizing ARE-containing mRNAs (PubMed:14688255, PubMed:17170118). Interacts (via phosphorylated form) with YWHAE (PubMed:21078877). Interacts (via C-terminus) with YWHAG; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAH; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAQ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with (via C-terminus) YWHAZ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Does not interact with SH3KBP1 (PubMed:20221403). Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is direct (By similarity). Interacts (via P-P-P-P-G repeats) with GIGYF2; the interaction is direct (PubMed:26763119). {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:14688255, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:17170118, ECO:0000269|PubMed:20221403, ECO:0000269|PubMed:20595389, ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:22844456, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:26763119}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11796723, ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:22844456}. Cytoplasm {ECO:0000269|PubMed:11796723, ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:17288565, ECO:0000269|PubMed:22844456, ECO:0000269|PubMed:24733888, ECO:0000269|PubMed:9703499}. Cytoplasmic granule {ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15967811}. Cytoplasm, P-body {ECO:0000269|PubMed:15967811}. Note=Shuttles between nucleus and cytoplasm in a CRM1-dependent manner (PubMed:11796723, PubMed:11886850). Localized predominantly in the cytoplasm in a p38 MAPK- and YWHAB-dependent manner (PubMed:11886850, PubMed:16508015). Colocalizes with SH3KBP1 and MAP3K4 in the cytoplasm (By similarity). Component of cytoplasmic stress granules (SGs) (PubMed:15967811). Localizes to cytoplasmic stress granules upon energy starvation (PubMed:15014438). Localizes in processing bodies (PBs) (By similarity). Excluded from stress granules in a phosphorylation MAPKAPK2-dependent manner (PubMed:15014438). Shuttles in and out of both cytoplasmic P-body and SGs (PubMed:15967811). {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11796723, ECO:0000269|PubMed:11886850, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15967811, ECO:0000269|PubMed:16508015}.

Tissue specificity: Expressed in skeletal muscle satellite cells (PubMed:25815583). Strongly expressed in differentiated adipocytes compared to preadipocytes (at protein level) (PubMed:22701344). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed in heart, placenta, kidney, intestine, liver, lung, thymus, fat and spleen (PubMed:2204625, PubMed:1699942). {ECO:0000269|PubMed:1699942, ECO:0000269|PubMed:2204625, ECO:0000269|PubMed:22701344, ECO:0000269|PubMed:24733888, ECO:0000269|PubMed:25815583}.

Induction: Up-regulated during adipocyte differentiation (PubMed:17288565, PubMed:22701344). Up-regulated transiently in response to fibroblast growth factor FGF4 in a MAPK-dependent manner in embryonic stem cells (ESCs) (PubMed:24733888). Up-regulated by interferons and/or lipopolysaccharide (LPS) in a STAT1- and p38 MAPK- dependent manner (PubMed:11533235, PubMed:16514065, PubMed:16508014, PubMed:16508015). Down-regulated in muscle satellite cells upon muscle injury (at protein level) (PubMed:25815583). Up-regulated by various mitogens (PubMed:7559666). Up-regulated by LPS and TNF-alpha (PubMed:9703499). Up-regulated by interferon IFN-gamma and/or LPS in a STAT1- and p38 MAPK-dependent manner (PubMed:15187092, PubMed:16514065). Up-regulated during adipocyte differentiation (PubMed:22701344). Up-regulated in keratinocytes during epidermal repair after wound healing (PubMed:20166898). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583). {ECO:0000269|PubMed:11533235, ECO:0000269|PubMed:15187092, ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:16514065, ECO:0000269|PubMed:17288565, ECO:0000269|PubMed:20166898, ECO:0000269|PubMed:22701344, ECO:0000269|PubMed:23046558, ECO:0000269|PubMed:24733888, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:7559666, ECO:0000269|PubMed:9703499}.

Domain: The C3H1-type zinc finger domains are necessary for ARE-binding activity. {ECO:0000250|UniProtKB:P26651}.

Ptm: Phosphorylated (PubMed:11533235). Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner (PubMed:11533235). Phosphorylated by MAPKAPK2 at Ser-52 and Ser-178; 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 (PubMed:15014438, PubMed:14688255, PubMed:16508014, PubMed:16508015, PubMed:17170118, PubMed:20595389, PubMed:21078877). Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding (PubMed:20595389, PubMed:21078877). 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 (PubMed:25815583). Phosphorylated by MAPK1 upon mitogen stimulation (PubMed:7768935, PubMed:14688255). Phosphorylated at Ser-58 and Ser-85; these phosphorylations increase in a SH3KBP1-dependent manner (By similarity). Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner (By similarity). Phosphorylation at Ser-52 may participate in the PKM- mediated degradation of ZFP36 in a p38 MAPK-dependent manner (By similarity). Dephosphorylated by serine/threonine phosphatase 2A at Ser-178 (PubMed:11533235, PubMed:17170118). {ECO:0000250|UniProtKB:P26651, ECO:0000269|PubMed:11533235, ECO:0000269|PubMed:14688255, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:16508015, ECO:0000269|PubMed:17170118, ECO:0000269|PubMed:20595389, ECO:0000269|PubMed:21078877, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:7768935}.

Ptm: Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway. {ECO:0000250|UniProtKB:P26651}.

Disruption phenotype: Mice appear normal at birth, but within 1-8 weeks after birth they develop a complex syndrome of cachexia, arthritis, autoimmunity, myeloid hyperplasia and general inflammation (PubMed:8630730). Show precocious skeletal muscle satellite cell activation and increased satellite cell fusion into myofibers (PubMed:25815583). Show higher levels of tumor necrosis factor (TNF)- alpha mRNA and protein in macrophages and an excess of circulating TNF- alpha (PubMed:8630730, PubMed:9703499, PubMed:16508014). Show higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in macrophages and an excess of GM-CSF secretion upon lipopolysaccharide (LPS) stimulation (PubMed:10706852). Show higher levels of serine/threonine-protein kinase PLK3 expression in macrophages (PubMed:19188452). Show higher levels of interleukin IL2 expression in splenocytes and T lymphocytes and an excess of IL2 secretion upon T cell activation (PubMed:15634918). Show an increase in the stability of numerous mRNAs, such as TNF-alpha, GM-CSF, IL2 and PLK3 mRNAs (PubMed:9703499, PubMed:10706852, PubMed:15634918, PubMed:17030620, PubMed:19188452). Show an absence of ARE-containing transcript deadenylation (PubMed:10330172). Mice with a double knockout of ZFP36 and MAPKAPK2 show increased amounts of TNF in macrophages almost comparable to single ZFP36 knockout (PubMed:16508014). {ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10706852, ECO:0000269|PubMed:15634918, ECO:0000269|PubMed:16508014, ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:19188452, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:8630730, ECO:0000269|PubMed:9703499}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Zinc-finger RNA-binding protein that destabilizes numerous 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:10330172, PubMed:10706852, PubMed:10805719, PubMed:15014438, PubMed:15187092, PubMed:15634918, PubMed:17030620, PubMed:19188452, PubMed:20595389, PubMed:21078877, PubMed:22701344, PubMed:27193233). Acts as an 3'- untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:21278420). Recruits deadenylase CNOT7 (and probably the CCR4- NOT complex) via association with CNOT1, and hence promotes ARE- mediated mRNA deadenylation (PubMed:21278420). Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:21278420). Self regulates by destabilizing its own mRNA (PubMed:15187092, PubMed:17288565). Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:11533235, PubMed:15187092, PubMed:16508014, PubMed:17288565, PubMed:17971298, PubMed:20595389, PubMed:21078877, PubMed:21278420, PubMed:22701344, PubMed:27193233). 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 (PubMed:8630730, PubMed:9703499, PubMed:15014438, PubMed:16514065). Plays also 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 (By similarity). Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (By similarity). Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA (PubMed:25815583). Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post- transcriptional level, such as MHC class I mRNAs (By similarity). Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs (By similarity). May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro (By similarity). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing (PubMed:22844456). Negatively regulates nuclear poly(A)- binding protein PABPN1-stimulated polyadenylation activity on ARE- containing pre-mRNA during LPS-stimulated macrophages (PubMed:22844456). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (By similarity). {ECO:0000250\|UniProtKB:P26651, ECO:0000269\|PubMed:10330172, ECO:0000269\|PubMed:10706852, ECO:0000269\|PubMed:10805719, ECO:0000269\|PubMed:11533235, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:15187092, ECO:0000269\|PubMed:15634918, ECO:0000269\|PubMed:15967811, ECO:0000269\|PubMed:16508014, ECO:0000269\|PubMed:16514065, ECO:0000269\|PubMed:17030620, ECO:0000269\|PubMed:17288565, ECO:0000269\|PubMed:17971298, ECO:0000269\|PubMed:19188452, ECO:0000269\|PubMed:20595389, ECO:0000269\|PubMed:21078877, ECO:0000269\|PubMed:21278420, ECO:0000269\|PubMed:22701344, ECO:0000269\|PubMed:22844456, ECO:0000269\|PubMed:25815583, ECO:0000269\|PubMed:27193233, ECO:0000269\|PubMed:8630730, ECO:0000269\|PubMed:9703499}.


Subunit:		Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:20595389, PubMed:21078877). Part of a mRNA decay activation complex at least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes DCP1A and DCP2 (By similarity). Associates with the RNA exosome complex (By similarity). Interacts (via phosphorylated form) with 14-3-3 proteins; these interactions promote exclusion of ZFP36 from cytoplasmic stress granules in response to arsenite treatment in a MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation and decay processes (PubMed:15014438, PubMed:20595389). Interacts with 14-3-3 proteins; these interactions occur in response to rapamycin in an Akt-dependent manner (By similarity). Interacts with AGO2 and AGO4 (By similarity). Interacts (via C-terminus) with CNOT1; this interaction occurs in a RNA-independent manner and induces mRNA deadenylation (PubMed:21278420). Interacts (via N-terminus) with CNOT6 (By similarity). Interacts with CNOT6L (PubMed:21078877). Interacts (via C-terminus) with CNOT7; this interaction occurs in a RNA- independent manner, induces mRNA deadenylation and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389, PubMed:21278420). Interacts (via unphosphorylated form) with CNOT8; this interaction occurs in a RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389). Interacts with DCP1A (By similarity). Interacts (via N-terminus) with DCP2 (By similarity). Interacts with EDC3 (By similarity). Interacts (via N-terminus) with EXOSC2 (By similarity). Interacts with heat shock 70 kDa proteins (By similarity). Interacts with KHSRP; this interaction increases upon cytokine-induced treatment (By similarity). Interacts with MAP3K4; this interaction enhances the association with SH3KBP1/CIN85 (By similarity). Interacts with MAPKAPK2; this interaction occurs upon skeletal muscle satellite cell activation (PubMed:25815583). Interacts with NCL (By similarity). Interacts with NUP214; this interaction increases upon lipopolysaccharide (LPS) stimulation (By similarity). Interacts with PABPC1; this interaction occurs in a RNA-dependent manner (PubMed:20595389, PubMed:21078877). Interacts (via hypophosphorylated form) with PABPN1 (via RRM domain and C-terminal arginine-rich region); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single- stranded poly(A) RNA-oligomer and in a p38 MAPK-dependent-manner and inhibits nuclear poly(A) tail synthesis (PubMed:22844456). Interacts with PAN2 (PubMed:21078877). Interacts (via C3H1-type zinc finger domains) with PKM (By similarity). Interacts (via C3H1-type zinc finger domains) with nuclear RNA poly(A) polymerase (PubMed:22844456). Interacts with PPP2CA; this interaction occurs in LPS-stimulated cells and induces ZFP36 dephosphorylation, and hence may promote ARE- containing mRNAs decay (PubMed:17170118). Interacts (via C-terminus) with PRR5L (via C-terminus); this interaction may accelerate ZFP36- mediated mRNA decay during stress (By similarity). Interacts (via C- terminus) with SFN; this interaction occurs in a phosphorylation- dependent manner (PubMed:11886850). Interacts (via extreme C-terminal region) with SH3KBP1/CIN85 (via SH3 domains); this interaction enhances MAP3K4-induced phosphorylation of ZFP36 at Ser-58 and Ser-85 and does not alter neither ZFP36 binding to ARE-containing transcripts nor TNF- alpha mRNA decay (By similarity). Interacts with XRN1 (By similarity). Interacts (via C-terminus and Ser-178 phosphorylated form) with YWHAB; this interaction occurs in a p38/MAPKAPK2-dependent manner, increases cytoplasmic localization of ZFP36 and protects ZFP36 from Ser-178 dephosphorylation by serine/threonine phosphatase 2A, and hence may be crucial for stabilizing ARE-containing mRNAs (PubMed:14688255, PubMed:17170118). Interacts (via phosphorylated form) with YWHAE (PubMed:21078877). Interacts (via C-terminus) with YWHAG; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAH; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAQ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with (via C-terminus) YWHAZ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Does not interact with SH3KBP1 (PubMed:20221403). Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is direct (By similarity). Interacts (via P-P-P-P-G repeats) with GIGYF2; the interaction is direct (PubMed:26763119). {ECO:0000250\|UniProtKB:P26651, ECO:0000269\|PubMed:11886850, ECO:0000269\|PubMed:14688255, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:17170118, ECO:0000269\|PubMed:20221403, ECO:0000269\|PubMed:20595389, ECO:0000269\|PubMed:21078877, ECO:0000269\|PubMed:21278420, ECO:0000269\|PubMed:22844456, ECO:0000269\|PubMed:25815583, ECO:0000269\|PubMed:26763119}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11796723, ECO:0000269\|PubMed:11886850, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:16508015, ECO:0000269\|PubMed:22844456}. Cytoplasm {ECO:0000269\|PubMed:11796723, ECO:0000269\|PubMed:11886850, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:16508015, ECO:0000269\|PubMed:17288565, ECO:0000269\|PubMed:22844456, ECO:0000269\|PubMed:24733888, ECO:0000269\|PubMed:9703499}. Cytoplasmic granule {ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:15967811}. Cytoplasm, P-body {ECO:0000269\|PubMed:15967811}. Note=Shuttles between nucleus and cytoplasm in a CRM1-dependent manner (PubMed:11796723, PubMed:11886850). Localized predominantly in the cytoplasm in a p38 MAPK- and YWHAB-dependent manner (PubMed:11886850, PubMed:16508015). Colocalizes with SH3KBP1 and MAP3K4 in the cytoplasm (By similarity). Component of cytoplasmic stress granules (SGs) (PubMed:15967811). Localizes to cytoplasmic stress granules upon energy starvation (PubMed:15014438). Localizes in processing bodies (PBs) (By similarity). Excluded from stress granules in a phosphorylation MAPKAPK2-dependent manner (PubMed:15014438). Shuttles in and out of both cytoplasmic P-body and SGs (PubMed:15967811). {ECO:0000250\|UniProtKB:P26651, ECO:0000269\|PubMed:11796723, ECO:0000269\|PubMed:11886850, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:15967811, ECO:0000269\|PubMed:16508015}.
Tissue specificity:		Expressed in skeletal muscle satellite cells (PubMed:25815583). Strongly expressed in differentiated adipocytes compared to preadipocytes (at protein level) (PubMed:22701344). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed in heart, placenta, kidney, intestine, liver, lung, thymus, fat and spleen (PubMed:2204625, PubMed:1699942). {ECO:0000269\|PubMed:1699942, ECO:0000269\|PubMed:2204625, ECO:0000269\|PubMed:22701344, ECO:0000269\|PubMed:24733888, ECO:0000269\|PubMed:25815583}.
Induction:		Up-regulated during adipocyte differentiation (PubMed:17288565, PubMed:22701344). Up-regulated transiently in response to fibroblast growth factor FGF4 in a MAPK-dependent manner in embryonic stem cells (ESCs) (PubMed:24733888). Up-regulated by interferons and/or lipopolysaccharide (LPS) in a STAT1- and p38 MAPK- dependent manner (PubMed:11533235, PubMed:16514065, PubMed:16508014, PubMed:16508015). Down-regulated in muscle satellite cells upon muscle injury (at protein level) (PubMed:25815583). Up-regulated by various mitogens (PubMed:7559666). Up-regulated by LPS and TNF-alpha (PubMed:9703499). Up-regulated by interferon IFN-gamma and/or LPS in a STAT1- and p38 MAPK-dependent manner (PubMed:15187092, PubMed:16514065). Up-regulated during adipocyte differentiation (PubMed:22701344). Up-regulated in keratinocytes during epidermal repair after wound healing (PubMed:20166898). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583). {ECO:0000269\|PubMed:11533235, ECO:0000269\|PubMed:15187092, ECO:0000269\|PubMed:16508014, ECO:0000269\|PubMed:16508015, ECO:0000269\|PubMed:16514065, ECO:0000269\|PubMed:17288565, ECO:0000269\|PubMed:20166898, ECO:0000269\|PubMed:22701344, ECO:0000269\|PubMed:23046558, ECO:0000269\|PubMed:24733888, ECO:0000269\|PubMed:25815583, ECO:0000269\|PubMed:7559666, ECO:0000269\|PubMed:9703499}.
Domain:		The C3H1-type zinc finger domains are necessary for ARE-binding activity. {ECO:0000250\|UniProtKB:P26651}.
Ptm:		Phosphorylated (PubMed:11533235). Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner (PubMed:11533235). Phosphorylated by MAPKAPK2 at Ser-52 and Ser-178; 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 (PubMed:15014438, PubMed:14688255, PubMed:16508014, PubMed:16508015, PubMed:17170118, PubMed:20595389, PubMed:21078877). Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding (PubMed:20595389, PubMed:21078877). 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 (PubMed:25815583). Phosphorylated by MAPK1 upon mitogen stimulation (PubMed:7768935, PubMed:14688255). Phosphorylated at Ser-58 and Ser-85; these phosphorylations increase in a SH3KBP1-dependent manner (By similarity). Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner (By similarity). Phosphorylation at Ser-52 may participate in the PKM- mediated degradation of ZFP36 in a p38 MAPK-dependent manner (By similarity). Dephosphorylated by serine/threonine phosphatase 2A at Ser-178 (PubMed:11533235, PubMed:17170118). {ECO:0000250\|UniProtKB:P26651, ECO:0000269\|PubMed:11533235, ECO:0000269\|PubMed:14688255, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:16508014, ECO:0000269\|PubMed:16508015, ECO:0000269\|PubMed:17170118, ECO:0000269\|PubMed:20595389, ECO:0000269\|PubMed:21078877, ECO:0000269\|PubMed:25815583, ECO:0000269\|PubMed:7768935}.
Ptm:		Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway. {ECO:0000250\|UniProtKB:P26651}.
Disruption phenotype:		Mice appear normal at birth, but within 1-8 weeks after birth they develop a complex syndrome of cachexia, arthritis, autoimmunity, myeloid hyperplasia and general inflammation (PubMed:8630730). Show precocious skeletal muscle satellite cell activation and increased satellite cell fusion into myofibers (PubMed:25815583). Show higher levels of tumor necrosis factor (TNF)- alpha mRNA and protein in macrophages and an excess of circulating TNF- alpha (PubMed:8630730, PubMed:9703499, PubMed:16508014). Show higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in macrophages and an excess of GM-CSF secretion upon lipopolysaccharide (LPS) stimulation (PubMed:10706852). Show higher levels of serine/threonine-protein kinase PLK3 expression in macrophages (PubMed:19188452). Show higher levels of interleukin IL2 expression in splenocytes and T lymphocytes and an excess of IL2 secretion upon T cell activation (PubMed:15634918). Show an increase in the stability of numerous mRNAs, such as TNF-alpha, GM-CSF, IL2 and PLK3 mRNAs (PubMed:9703499, PubMed:10706852, PubMed:15634918, PubMed:17030620, PubMed:19188452). Show an absence of ARE-containing transcript deadenylation (PubMed:10330172). Mice with a double knockout of ZFP36 and MAPKAPK2 show increased amounts of TNF in macrophages almost comparable to single ZFP36 knockout (PubMed:16508014). {ECO:0000269\|PubMed:10330172, ECO:0000269\|PubMed:10706852, ECO:0000269\|PubMed:15634918, ECO:0000269\|PubMed:16508014, ECO:0000269\|PubMed:17030620, ECO:0000269\|PubMed:19188452, ECO:0000269\|PubMed:25815583, ECO:0000269\|PubMed:8630730, ECO:0000269\|PubMed:9703499}.