Activation of PPARγ Coactivator-1 Through Transcription Factor Docking

作者：Pere Puigserver, Guillaume Adelmant, Zhidan Wu, Melina Fan, Jianming Xu, Bert W. O’Malley, Bruce M. Spiegelman · 发表于：Science · 年份：1999 · DOI：10.1126/science.286.5443.1368 · 被引用次数：598 · 研究领域：Peroxisome Proliferator-Activated Receptors、Adipose Tissue and Metabolism、Estrogen and related hormone effects

Transcriptional coactivators have been viewed as constitutively active components, using transcription factors mainly to localize their functions. Here, it is shown that PPARgamma coactivator-1 (PGC-1) promotes transcription through the assembly of a complex that includes the histone acetyltransferases steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP)/p300. PGC-1 has a low inherent transcriptional activity when it is not bound to a transcription factor. The docking of PGC-1 to peroxisome proliferator-activated receptor gamma (PPARgamma) stimulates an apparent conformational change in PGC-1 that permits binding of SRC-1 and CBP/p300, resulting in a large increase in transcriptional activity. Thus, transcription factor docking switches on the activity of a coactivator protein.