Recombinant Human Tristetraprolin/TTP protein

Specifications

Form

Liquid

General info

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 : 10330172, PubMed : 10751406, PubMed : 11279239, PubMed : 12115244, PubMed : 12748283, PubMed : 15187101, PubMed : 15634918, PubMed : 16702957, PubMed : 17030620, PubMed : 20221403, PubMed : 20702587, PubMed : 21775632, PubMed : 23644599, PubMed : 25815583, PubMed : 27193233, PubMed : 31439631, PubMed : 9703499). 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 : 16702957, PubMed : 17030620, PubMed : 19188452, PubMed : 20221403, PubMed : 20702587, 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).. (Microbial infection) Negatively regulates HTLV-1 TAX-dependent transactivation of viral long terminal repeat (LTR) promoter.

Post-translational modifications

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).

Subcellular localisation

Nucleus