Maganti Nagini, Moody Tomika D, Truax Agnieszka D, Thakkar Meghna, Spring Alexander M, Germann Markus W, Greer Susanna F
Graduate Program in Cell Biology and Immunology, Department of Biology, Georgia State University, Atlanta, Georgia, United States of America.
Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America.
PLoS One. 2014 Mar 13;9(3):e91200. doi: 10.1371/journal.pone.0091200. eCollection 2014.
Accumulating evidence shows the 26S proteasome is involved in the regulation of gene expression. We and others have demonstrated that proteasome components bind to sites of gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear, although prior observations suggest both proteolytic and non-proteolytic activities. Here, we define novel, non-proteolytic, roles for each of the three 19S heterodimers, represented by the 19S ATPases Sug1, S7, and S6a, in mammalian gene expression using the inflammatory gene CIITApIV. These 19S ATPases are recruited to induced CIITApIV promoters and also associate with CIITA coding regions. Additionally, these ATPases interact with elongation factor PTEFb complex members CDK9 and Hexim-1 and with Ser5 phosphorylated RNA Pol II. Both the generation of transcripts from CIITApIV and efficient recruitment of RNA Pol II to CIITApIV are negatively impacted by siRNA mediated knockdown of these 19S ATPases. Together, these results define novel roles for 19S ATPases in mammalian gene expression and indicate roles for these ATPases in promoting transcription processes.
越来越多的证据表明，26S蛋白酶体参与基因表达的调控。我们和其他人已经证明，蛋白酶体成分与基因转录位点结合，调节组蛋白的共价修饰，并参与哺乳动物细胞中激活复合物的组装。尽管先前的观察表明蛋白酶体具有蛋白水解和非蛋白水解活性，但其影响转录的机制仍不清楚。在这里，我们利用炎症基因CIITApIV，定义了由19S ATP酶Sug1、S7和S6a代表的三种19S异二聚体在哺乳动物基因表达中的新的非蛋白水解作用。这些19S ATP酶被招募到诱导的CIITApIV启动子上，并与CIITA编码区相关联。此外，这些ATP酶与延伸因子PTEFb复合物成员CDK9和Hexim-1以及与Ser5磷酸化的RNA Pol II相互作用。CIITApIV转录本的产生以及RNA Pol II向CIITApIV的有效募集都受到这些19S ATP酶的siRNA介导的敲低的负面影响。总之，这些结果定义了19S ATP酶在哺乳动物基因表达中的新作用，并表明这些ATP酶在促进转录过程中的作用。
