Two contact regions between Stat1 and CBP/p300 in interferon γ signaling

• DOI: 10.1073/pnas.93.26.15092
• Publication Date: 2002-07-26T14:43:20Z
• Authors: Jue J. Zhang; Uwe Vinkemeier; Wei Gu; Debabrata Chakrav...; Curt M. Horvath; James E. Darnell
• Keywords: Transcriptional Activation; 0301 basic medicine; Osteosarcoma; Transcription, Genetic; Recombinant Fusion Proteins; Nuclear Proteins; Transfection; CREB-Binding Protein; Cell Line; 3. Good health; DNA-Binding Proteins; Interferon-gamma; 03 medical and health sciences; STAT1 Transcription Factor; Trans-Activators; Animals; Humans; Adenovirus E1A Proteins; Phosphorylation; Glutathione Transferase; Signal Transduction; Transcription Factors

Interferon γ (IFN-γ) induces rapid tyrosine phosphorylation of the latent cytoplasmic transcription factor, Stat1, which then forms homodimers, translocates to the nucleus and participates in IFN-γ-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-γ-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-γ is based at least in part on direct competition by nuclear Stat1 with E1A for CBP/p300 binding.