interferon-gamma activated factor; gamma-activated factor; signal transducer & activator of transcription-1 (STAT1)
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Function
- signal transducer & activator of transcription
- tumor suppressor
- mediates signaling by interferons (IFNs)
- following IFN type-1 (IFN-alpha & IFN-beta) binding to cell surface receptors, Jak kinases (TYK2 & JAK1) are activated, leading to Tyr phosphorylation of STAT1 & STAT2
- the phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus
- ISGF3 binds to the IFN-stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state
- in response to IFN type-2 (IFN-gamma), STAT1 is Tyr- & Ser- phosphorylated
- it then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus & binds to the IFN gamma activated sequence (GAS) to drive the expression of target genes, inducing a cellular antiviral state
- isoform alpha homodimerizes upon IFN-gamma induced phosphorylation
- heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation
- forms heterodimer with STAT3
- interacts with NMI
- interacts with Sendai virus C', C, Y1 & Y2 proteins, Nipah virus P, V & W proteins, & rabies virus phosphoprotein preventing activation of ISRE & GAS promoter (putative)
- interaction with HCV core protein results in STAT1 degradation
- phosphorylated on Tyr in response to IFN-alpha, IFN-gamma, PDGF & EGF
- Ser phosphorylation is also required for maximal transcriptional activity in IFN-gamma transduction (lacking in beta form)
- also activated by IL-6 & CNTF[4]
Structure
- belongs to the transcription factor STAT family
- contains 1 SH2 domain
Compartment
Alternative splicing
named isoforms=2
Pathology
- defects in STAT1 are the cause
More general terms
- DNA-binding protein
- signal transducer & activator of transcription (STAT)
- anti-oncoprotein (tumor suppressor protein)
Additional terms
Component of
References
- ↑ Shuai K, Schindler C, Prezioso VR, Darnell JE Jr. Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992 Dec 11;258(5089):1808-12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1281555
- ↑ Montminy M. Trying on a new pair of SH2s. Science. 1993 Sep 24;261(5129):1694-5. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8397444
- ↑ Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8048164
- ↑ 4.0 4.1 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=6772
- ↑ TAT1base; Note: STAT1 mutation db http://bioinf.uta.fi/STAT1base/
- ↑ Wikipedia; Note: STAT1 entry http://en.wikipedia.org/wiki/STAT1
- ↑ UniProt http://www.uniprot.org/uniprot/P42224.html