ZFP36L2
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:14981510, PubMed:25106868, PubMed:34611029). 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:14981510, PubMed:20506496, PubMed:25106868). 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.
Involvement in disease
Oocyte/zygote/embryo maturation arrest 13
OZEMA13
An autosomal recessive female infertility disorder characterized by embryonic development arrest and embryo implantation failure.
None
The disease is caused by variants affecting the gene represented in this entry.
A frameshift mutation disrupting ZFP36L2 have been found in a patient with acute myeloid leukemia, suggesting that defective ZFP36L2 might be involved in the pathogenesis of certain types of hematological cancers (PubMed:21109922).
Post-translational modifications
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).
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 oocytes (PubMed:34611029).
Cellular localization
- Nucleus
- Cytoplasm
- Shuttles between the nucleus and the cytoplasm in a XPO1/CRM1-dependent manner.
Alternative names
ERF2, RNF162C, TIS11D, ZFP36L2, mRNA decay activator protein ZFP36L2, Butyrate response factor 2, EGF-response factor 2, TPA-induced sequence 11d, ERF-2, ZFP36-like 2