Horvai A E, Xu L, Korzus E, Brard G, Kalafus D, Mullen T M, Rose D W, Rosenfeld M G, Glass C K
Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla 92093-0651, USA.
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1074-9. 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.
我们报告，干扰素γ（IFN-γ）通过拮抗AP-1的Ras依赖性活性和协同ets结构域转录因子来抑制巨噬细胞清道夫受体基因的转录，这显然是由于AP-1/ets因子与活化的STAT1之间竞争有限量的CBP和p300所致。与该模型一致，STAT1α在细胞中直接与CBP相互作用，显微注射抗CBP和抗p300抗体可阻断对IFN-γ的转录反应。缺乏STAT1的细胞无法抑制AP-1/ets活性，CBP的过表达既增强了IFN-γ依赖性转录，又减轻了AP-1/ets的抑制作用。因此，CBP和p300通过作为STAT1α的必需共激活因子，整合IFN-γ对基因表达的正负效应，调节对两个或更多信号转导途径同时激活的基因特异性反应。
