Ge H, Zhao Y, Chait B T, Roeder R G
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12691-5. doi: 10.1073/pnas.91.26.12691.
Human positive cofactor 4 (PC4) mediates activator-dependent transcription by RNA polymerase II, apparently through interactions with transcriptional activators and the basal transcription machinery. We report here that PC4 function is modulated by in vivo phosphorylation. Protein-protein interaction studies and in vitro transcription assays demonstrate that only the nonphosphorylated form of PC4 is functionally active. Although recombinant PC4 can be phosphorylated by casein kinase II and protein kinase C in vitro, mutational and mass spectrometric analyses suggest that the in vivo hyperphosphorylation of PC4 is mediated mainly by casein kinase II and restricted to an N-terminal serine-rich region. These observations provide one example of a transcriptional cofactor that is negatively regulated by casein kinase II phosphorylation.
人正向辅因子4（PC4）介导RNA聚合酶II依赖激活因子的转录，显然是通过与转录激活因子和基础转录机制相互作用来实现的。我们在此报告，PC4的功能受体内磷酸化调节。蛋白质-蛋白质相互作用研究和体外转录分析表明，只有PC4的非磷酸化形式具有功能活性。虽然重组PC4在体外可被酪蛋白激酶II和蛋白激酶C磷酸化，但突变分析和质谱分析表明，PC4在体内的过度磷酸化主要由酪蛋白激酶II介导，且局限于富含丝氨酸的N端区域。这些观察结果提供了一个转录辅因子受酪蛋白激酶II磷酸化负调控的例子。
