Nawaz Zafar, O'Malley Bert W
Cancer Center, Creighton University, Omaha, Nebraska 68178, USA.
Mol Endocrinol. 2004 Mar;18(3):493-9. doi: 10.1210/me.2003-0388. Epub 2003 Dec 12.
The importance of the ubiquitin proteasome pathway in higher eukaryotes has been well established in cell cycle regulation, signal transduction, and cell differentiation, but has only recently been linked to nuclear hormone receptor-regulated gene transcription. Characterization of a number of ubiquitin proteasome pathway enzymes as coactivators and observations that several nuclear receptors are ubiquitinated and degraded in the course of their nuclear activities provide evidence that ubiquitin proteasome-mediated protein degradation plays an integral role in eukaryotic transcription. In addition to receptors, studies have revealed that coactivators are ubiquitinated and degraded via the proteasome. The notion that the ubiquitin proteasome pathway is involved in gene transcription is further strengthened by the fact that ubiquitin proteasome pathway enzymes are recruited to the promoters of target genes and that proteasome-dependent degradation of nuclear receptors is required for efficient transcriptional activity. These findings suggest that protein degradation is coupled with nuclear receptor coactivation activity. It is possible that the ubiquitin proteasome pathway modulates transcription by promoting remodeling and turnover of the nuclear receptor-transcription complex. In this review, we discus the possible role of the ubiquitin proteasome pathway in nuclear hormone receptor-regulated gene transcription.
泛素蛋白酶体途径在高等真核生物中的重要性已在细胞周期调控、信号转导和细胞分化方面得到充分证实，但直到最近才与核激素受体调节的基因转录联系起来。一些泛素蛋白酶体途径的酶被鉴定为共激活因子，以及观察到几种核受体在其核活性过程中被泛素化并降解，这些都证明泛素蛋白酶体介导的蛋白质降解在真核转录中起着不可或缺的作用。除了受体，研究还表明共激活因子也会通过蛋白酶体被泛素化并降解。泛素蛋白酶体途径参与基因转录这一观点因以下事实而得到进一步加强：泛素蛋白酶体途径的酶被招募到靶基因的启动子上，并且核受体的蛋白酶体依赖性降解是高效转录活性所必需的。这些发现表明蛋白质降解与核受体共激活活性相关联。泛素蛋白酶体途径有可能通过促进核受体 - 转录复合物的重塑和周转来调节转录。在这篇综述中，我们讨论泛素蛋白酶体途径在核激素受体调节的基因转录中可能发挥的作用。
