Post-translational modification of activators

描述(申请人提供)：最近发现泛素/蛋白酶体途径的蛋白质与RNA聚合酶II的转录密切相关。我们证明，这六种蛋白酶体ATPase与其他因素协同作用，形成了一种称为APIs的复合体，对于有效的伸长是必不可少的。最近，我们发现在ATP存在的情况下，APIs复合体主动解离激活剂-DNA复合体，这一活性可能参与了激活剂功能的下调。这一发现为转录酶学开辟了一个有趣的新领域。特别有趣的是，这里提出的结果表明，激活剂单一泛素化可能是调节API介导的拆解反应效力的关键事件。确定激活子泛素化的机制作用(S)正在成为转录酶学中的一个主要问题。本项目将致力于更好地理解蛋白酶体ATPase(APIs复合体)对Gal4-DNA相互作用的负调控。泛素化和其他翻译后修饰对这一过程的影响将构成这些研究的中心部分。我们预计，这些研究将成为理解大量基因特异性转录因子活性的一个重要新方面的范例。

DESCRIPTION (provided by applicant): It has recently been found that proteins of the ubiquitin/proteasome pathway are involved intimately in RNA polymerase II transcription. We demonstrated that the six proteasomal ATPases in concert with other factors, form a complex called APIS that is essential for efficient elongation. More recently, we have found that the APIS complex actively dissociates activator-DNA complexes in the presence of ATP, an activity that may be involved in the down-regulation of activator function. This discovery opens an interesting new area of transcription enzymology. It is particularly interesting in light of results presented here that suggest activator mono-ubiquitylation may be a critical event in regulating the potency of the APIS-mediated disassembly reaction. Identifying the mechanistic role(s) for activator ubiquitylation is emerging as a major issue intranscription enzymology. This project will focus on better understanding the negative regulation of Gal4-DNA interactions by the proteasomal ATPases (APIS complex). The effect of ubiquitylation and perhaps other post-translational modifications on this process will constitute a central part of these investigations. We anticipate that these studies will emerge as a paradigm for understanding an important new aspect of the activity of a large percentage of gene-specific transcription factors.