ZFP36L2

ZFP36L2 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. ZFP36L2 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.

ZFP36 Ring Finger Protein Like 2

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:25106868, PubMed:14981510).
Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:25106868).
Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (PubMed:25106868).
Binds to 3'-UTR ARE of numerous mRNAs (PubMed:20506496, PubMed:25106868, PubMed:14981510).
Promotes ARE-containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868).
Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA. Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA. Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation. In association with ZFP36L1 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 process and functional immune cell formation. Together with ZFP36L1 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.

Biological Process 3'-UTR-mediated mRNA destabilization 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 transforming growth factor beta stimulus Source:UniProtKB1 Publication
Biological Process cellular response to tumor necrosis factor Source:UniProtKB1 Publication
Biological Process definitive hemopoiesis Source:UniProtKB
Biological Process ERK1 and ERK2 cascade Source:UniProtKB1 Publication
Biological Process hemopoiesis Source:UniProtKB
Biological Process mRNA catabolic process Source:UniProtKB
Biological Process negative regulation of fat cell differentiation Source:UniProtKB
Biological Process negative regulation of mitotic cell cycle phase transition Source:UniProtKB
Biological Process negative regulation of stem cell differentiation Source:UniProtKB
Biological Process nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:Ensembl
Biological Process positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source:UniProtKB
Biological Process regulation of B cell differentiation Source:UniProtKB
Biological Process regulation of mRNA stability Source:UniProtKB1 Publication
Biological Process response to wounding Source:UniProtKB1 Publication
Biological Process somatic stem cell division Source:UniProtKB
Biological Process somatic stem cell population maintenance Source:UniProtKB
Biological Process T cell differentiation in thymus Source:UniProtKB

Nucleus
Cytoplasm
Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner.

Defects in ZFP36L2 may be a cause of leukemias. Frameshift mutations disrupting ZFP36L2 have been found in a patient with acute myeloid leukemia (PubMed:21109922).

Phosphorylated by RPS6KA1 at Ser-490 and Ser-492 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 (LDL) receptor (LDLR) mRNA (PubMed:25106868).
Phosphorylation occurs during early preadipocyte differentiation (By similarity).