Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman B M
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Science. 1999 Nov 12;286(5443):1368-71. doi: 10.1126/science.286.5443.1368.
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.
转录共激活因子一直被视为组成型活性成分，主要利用转录因子来定位其功能。本文表明，过氧化物酶体增殖物激活受体γ共激活因子-1（PGC-1）通过组装一个包含组蛋白乙酰转移酶类固醇受体共激活因子-1（SRC-1）和CREB结合蛋白（CBP）/p300的复合物来促进转录。当PGC-1未与转录因子结合时，其固有转录活性较低。PGC-1与过氧化物酶体增殖物激活受体γ（PPARγ）对接会刺激PGC-1发生明显的构象变化，从而允许SRC-1和CBP/p300结合，导致转录活性大幅增加。因此，转录因子对接开启了共激活蛋白的活性。
