Post-translational modification of activators

描述（由申请人提供）：最近发现泛素/蛋白酶体途径的蛋白质密切参与RNA聚合酶II的转录。我们证明了六种蛋白酶体atp酶与其他因子一起形成了一种称为api的复合物，这是有效延伸所必需的。最近，我们发现api复合物在ATP存在的情况下积极地解离激活剂- dna复合物，这种活性可能参与激活剂功能的下调。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，根据本文提出的结果，激活剂单泛素化可能是调节api介导的分解反应效力的关键事件。识别激活剂泛素化的机制作用正在成为转录酶学的一个主要问题。本项目将专注于更好地理解蛋白酶体atp酶（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.