signal transducer & activator of transcription 3; acute-phase response factor (STAT3, APRF)
Jump to navigation
Jump to search
Function
- transcription factor
- involved in the gp130-mediated signaling pathway
- activated by IL-6
- binds to (IL6-responsive elements identified in promoters of various acute-phase protein genes
- activated by IL31 through IL31RA
- forms a homodimer or a heterodimer with STAT1
- interacts with NCOA1, PELP1, SOCS7 & STATIP1
- interacts with HCV core protein
- interacts with IL23R in presence of IL23
- interacts with IL31RA
- interacts with SIPAR
- Tyr phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, IFN-alpha & OSM
- phosphorylated on Ser upon DNA damage, probably by ATM or ATR
- Ser phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers & maximal transcriptional activity
- phosphorylation of STAT3 at Tyr-705 induces
- STAT3 dimerization
- nuclear translocation
- activation of gene transcription
- phosphorylation by CDK1 on Ser-727.[3]
- inhibits DNA-binding
- inhibits gene transcription
- may regulate M-phase
Structure
- belongs to the transcription factor STAT family
- contains 1 SH2 domain
Compartment
- cytoplasm, nucleus
- translocated into nucleus in response to phosphorylation
Alternative splicing
named isoforms=2
Expression
- heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
Pathology
- defects in STAT3 are the cause of hyperimmunoglobulin E
- mediates melanoma progression[4]
More general terms
Component of
References
- ↑ Zhang X, Blenis J, Li HC, Schindler C, Chen-Kiang S. Requirement of serine phosphorylation for formation of STAT- promoter complexes. Science. 1995 Mar 31;267(5206):1990-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7701321
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6774
- ↑ 3.0 3.1 Shi X, Zhang H, Paddon H, Lee G, Cao X, Pelech S. Phosphorylation of STAT3 serine-727 by cyclin-dependent kinase 1 is critical for nocodazole-induced mitotic arrest. Biochemistry. 2006 May 9;45(18):5857-67. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16669628
- ↑ 4.0 4.1 Wang W et al. STAT3 as a biomarker of progression in atypical nevi of patients with melanoma: Dose:response effects of systemic IFN therapy. J Invest Dermatol 2008 Aug; 128:1997. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18305569
- ↑ Wikipedia; Note: STAT3 entry http://en.wikipedia.org/wiki/STAT3
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/STAT3ID444.html
- ↑ Web: Name=SeattleSNPs http://pga.gs.washington.edu/data/stat3/
- ↑ UniProt http://www.uniprot.org/uniprot/P40763.html