TTP
a CCCH-type zinc finger protein that has anti-inflammatory activity. 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. Regulates inflammatory responses at the post-transcriptional level. TTP deficiency in mice causes a severe inflammatory syndrome that includes autoimmunity, myeloid hyperplasia, and erosive arthritis. Binds to and destabilizes mRNA molecules with AU-rich elements (AREs). Destabilizes tumor necrosis factor-alpha (TNF??), interleukin 2 (IL2), granulocyte-macrophage colony-stimulating factor (GM-CSF), transcription factor E47, and cyclooxygenase 2 (COX2) mRNAs. Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia. Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). TNF-alpha and GM-CSF mRNAs are stabilized in TTP-deficient mice, causing a severe inflammatory syndrome. Self regulates by destabilizing its own mRNA. In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing. Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages. Associates with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs. Participates with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs. Involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion. Conversely, high levels of TTP reduce inflammatory responses. TTP is a very low abundance protein that is rapidly induced by insulin, glucocorticoids, lipopolysaccharide (LPS), fetal calf serum, zinc, herpes simplex virus 1, green tea, and cinnamon. Once induced, the TTP protein is relatively stable. TTP is extensively phosphorylated. Note: This description may include information from UniProtKB.
Molecular Function: 14-3-3 protein binding; C-C chemokine binding; DNA binding; enzyme binding; heat shock protein binding; metal ion binding; mRNA 3'-UTR AU-rich region binding; mRNA binding; protein binding; protein kinase binding; protein-containing complex binding; RNA polymerase binding
Biological Process: 3'-UTR-mediated mRNA destabilization; 3'-UTR-mediated mRNA stabilization; cellular response to epidermal growth factor stimulus; cellular response to fibroblast growth factor stimulus; cellular response to glucocorticoid stimulus; cellular response to granulocyte macrophage colony-stimulating factor stimulus; cellular response to lipopolysaccharide; cellular response to tumor necrosis factor; hematopoietic stem cell differentiation; MAPK cascade; miRNA-mediated gene silencing by inhibition of translation; mRNA catabolic process; mRNA transport; myeloid cell differentiation; negative regulation of erythrocyte differentiation; negative regulation of hematopoietic stem cell differentiation; negative regulation of inflammatory response; negative regulation of interleukin-2 production; negative regulation of polynucleotide adenylyltransferase activity; negative regulation of transcription by RNA polymerase II; negative regulation of viral transcription; nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; nuclear-transcribed mRNA catabolic process, deadenylation-independent decay; nuclear-transcribed mRNA poly(A) tail shortening; p38MAPK cascade; positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA; positive regulation of fat cell differentiation; positive regulation of intracellular mRNA localization; positive regulation of miRNA-mediated gene silencing; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; regulation of keratinocyte apoptotic process; regulation of keratinocyte differentiation; regulation of keratinocyte proliferation; regulation of mRNA stability; regulation of tumor necrosis factor production; response to starvation; response to wounding
