ZFP36L1

This gene is a member of the TIS11 family of early response genes. Family members are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. The gene is well conserved across species and has a promoter that contains motifs seen in other early-response genes. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This putative nuclear transcription factor most likely functions in regulating the response to growth factors. [provided by RefSeq]

zinc finger protein 36, C3H type-like 1

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:15538381, PubMed:15467755, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25106868, PubMed:25014217, 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:15538381, PubMed:15467755, PubMed:17030608, PubMed:19179481, PubMed:20702587, PubMed:24700863, PubMed:25106868, PubMed:25014217, 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).

Biological Process 3'-UTR-mediated mRNA destabilization Source:UniProtKB7 Publications
Biological Process apoptotic process Source:Ensembl
Biological Process cell population proliferation Source:Ensembl
Biological Process cellular response to cAMP 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:UniProtKB
Biological Process cellular response to glucocorticoid stimulus Source:UniProtKB1 Publication
Biological Process cellular response to hypoxia Source:UniProtKB1 Publication
Biological Process cellular response to insulin stimulus Source:UniProtKB1 Publication
Biological Process cellular response to peptide hormone stimulus Source:UniProtKB2 Publications
Biological Process cellular response to raffinose Source:UniProtKB
Biological Process cellular response to salt stress Source:UniProtKB
Biological Process cellular response to transforming growth factor beta stimulus Source:UniProtKB1 Publication
Biological Process cellular response to tumor necrosis factor Source:UniProtKB1 Publication
Biological Process chorio-allantoic fusion Source:Ensembl
Biological Process ERK1 and ERK2 cascade Source:UniProtKB1 Publication
Biological Process heart development Source:Ensembl
Biological Process MAPK cascade Source:UniProtKB2 Publications
Biological Process mesendoderm development Source:UniProtKB
Biological Process mRNA processing Source:UniProtKB-KW
Biological Process mRNA transport Source:UniProtKB1 Publication
Biological Process multicellular organism growth Source:Ensembl
Biological Process negative regulation of erythrocyte differentiation Source:UniProtKB1 Publication
Biological Process negative regulation of mitotic cell cycle phase transition Source:UniProtKB
Biological Process neural tube development Source:Ensembl
Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:Ensembl
Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-independent decay Source:UniProtKB
Biological Process p38MAPK cascade Source:UniProtKB
Biological Process phosphatidylinositol 3-kinase signaling 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 monocyte differentiation Source:UniProtKB1 Publication
Biological Process positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:UniProtKB
Biological Process proepicardium development Source:Ensembl
Biological Process protein kinase B signaling Source:UniProtKB
Biological Process regulation of B cell differentiation Source:UniProtKB
Biological Process regulation of gene expression 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 3'-end processing Source:UniProtKB1 Publication
Biological Process regulation of mRNA stability Source:UniProtKB8 Publications
Biological Process regulation of myoblast differentiation Source:UniProtKB
Biological Process regulation of stem cell proliferation Source:UniProtKB
Biological Process response to wounding Source:UniProtKB1 Publication
Biological Process spongiotrophoblast layer development Source:Ensembl
Biological Process T cell differentiation in thymus Source:UniProtKB
Biological Process vasculogenesis Source:Ensembl

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).

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).