title: Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling.
abstract: Interferon gamma (IFN-gamma) induces rapid tyrosine phosphorylation of the latent cytoplasmic transcription factor, Stat1, which then forms homodimers, translocates to the nucleus and participates in IFN-gamma-induced transcription. However, little is known of the interactions between Stat1 and the general transcription machinery during transcriptional activation. We show here that Stat1 can directly interact with the CREB-binding protein (CBP)/p300 family of transcriptional coactivators. Specifically, two interaction regions were identified: the amino-terminal region of Stat1 interacts with the CREB-binding domain of CBP/p300 and the carboxyl-terminal region of Stat1 interacts with the domain of CBP/p300 that binds adenovirus E1A protein. Transfection experiments suggest a role for these interactions in IFN-gamma-induced transcription. Because CBP/p300-binding is required for the adenovirus E1A protein to regulate transcription of many genes during viral replication and cellular transformation, it is possible that the anti-viral effect of IFN-gamma is based at least in part on direct competition by nuclear Stat1 with E1A for CBP/p300 binding.
authors.affiliation: Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Zhang
authors.forename: U
authors.initials: U
authors.lastname: Vinkemeier
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: D
authors.initials: D
authors.lastname: Chakravarti
authors.forename: C M
authors.initials: CM
authors.lastname: Horvath
authors.forename: J E
authors.initials: JE
authors.lastname: Darnell
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism*; D012516:Osteosarcoma; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D005982:Glutathione Transferase