Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300

作者：Horvai AE; Xu L; Korzus E; Brard G; Kalafus D; Mullen TM; Rose DW; Rosenfeld MG; Glass CK

来源：Proceedings of the National Academy of Sciences of the United States of America, 1997, 94(4): 1074-1079.

DOI：10.1073/pnas.94.4.1074

We report that interferon gamma (IFN-gamma) inhibits transcription of the macrophage scavenger receptor gene by antagonizing the Ras-dependent activities of AP-1 and cooperating ets domain transcription factors, apparently as a result of competition between AP-1/ets factors and activated STAT1 for limiting amounts of CBP and p300. Consistent with this model, STAT1 alpha interacts directly with CBP in cells, and microinjection of anti-CBP and anti-p300 antibodies blocks transcriptional responses to IFN-gamma, Cells lacking STAT1 fail to inhibit AP-1/ets activity, and overexpression of CBP both potentiates IFN-gamma-dependent transcription and relieves AP-1/ets repression, Thus, CBP and p300 integrate both positive and negative effects of IFN-gamma on gene expression by serving as essential coactivators of STAT1 alpha, modulating gene-specific responses to simultaneous activation of two or more signal transduction pathways.

• 出版日期1997-2-18