Schwartz Claudia, Beck Kristina, Mink Sigrun, Schmolke Mirco, Budde Bastian, Wenning Dorit, Klempnauer Karl-Heinz
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Strasse 2, D-48149 Münster, Germany.
EMBO J. 2003 Feb 17;22(4):882-92. doi: 10.1093/emboj/cdg076.
Transcriptional coactivators such as p300 act as crucial elements in the eukaryotic gene regulation network. These proteins bind to various transcription factors which recruit them to specific gene regions whose chromatin structure subsequently is remodeled. Previously, we have shown that C/EBPbeta recruits p300 by interacting with the E1A-binding site of the coactivator. We now show that C/EBPbeta not only binds to p300 but also triggers massive phosphorylation of p300. This novel activity of C/EBPbeta is dependent on the E1A-binding region of p300 as well as on several subdomains of C/EBPbeta, all of which are involved in the p300-C/EBPbeta interaction. We have identified several sites of C/EBPbeta-inducible phosphorylation within the C-terminal domain of p300. Mutation of these sites substantially impairs the activity of p300 as a coactivator of C/EBPbeta. Interestingly, phosphorylation of p300 is also triggered by other C/EBP family members as well as by various other transcription factors that interact with the E1A-binding domain of p300, suggesting that this novel phosphorylation mechanism may be of general relevance.
转录共激活因子如p300是真核基因调控网络中的关键元件。这些蛋白质与各种转录因子结合，转录因子将它们招募到特定的基因区域，随后这些区域的染色质结构会发生重塑。此前，我们已经表明C/EBPβ通过与共激活因子的E1A结合位点相互作用来招募p300。我们现在发现，C/EBPβ不仅与p300结合，还会引发p300的大量磷酸化。C/EBPβ的这种新活性依赖于p300的E1A结合区域以及C/EBPβ的几个亚结构域，所有这些都参与了p300与C/EBPβ的相互作用。我们已经确定了p300 C末端结构域内几个C/EBPβ诱导的磷酸化位点。这些位点的突变会严重损害p300作为C/EBPβ共激活因子的活性。有趣的是，p300的磷酸化也由其他C/EBP家族成员以及与p300的E1A结合结构域相互作用的各种其他转录因子触发，这表明这种新的磷酸化机制可能具有普遍意义。
