Chen Jianguang, Archer Trevor K
Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Mol Cell Biol. 2005 Oct;25(20):9016-27. doi: 10.1128/MCB.25.20.9016-9027.2005.
The mammalian SWI/SNF chromatin remodeling complex, whose function is of critical importance in transcriptional regulation, contains approximately 10 protein components. The expression levels of the core SWI/SNF subunits, including BRG1/Brm, BAF155, BAF170, BAF60, hSNF/Ini1, and BAF57, are stoichiometric, with few to no unbound molecules in the cell. Here we report that exogenous expression of the wild type or certain deletion mutants of BAF57, a key subunit that mediates the interaction between the remodeling complex and transcription factors, results in diminished expression of endogenous BAF57. This down-regulation process is mediated by an increase in proteasome-dependent degradation of the BAF57 protein. Furthermore, the protein levels of BAF155/170 dictate the maximum cellular amount of BAF57. We mapped the domains responsible for the interaction between BAF57 and BAF155 and demonstrated that protein-protein interactions between them play an important role in this regulatory process. These findings provide insights into the physiological mechanisms responsible for maintaining the proper stoichiometric levels of the protein components comprising multimeric enzyme complexes.
哺乳动物的SWI/SNF染色质重塑复合体在转录调控中起着至关重要的作用，它包含大约10种蛋白质成分。核心SWI/SNF亚基的表达水平，包括BRG1/Brm、BAF155、BAF170、BAF60、hSNF/Ini1和BAF57，是化学计量的，细胞中几乎没有未结合的分子。在此，我们报道，作为介导重塑复合体与转录因子相互作用的关键亚基，BAF57的野生型或某些缺失突变体的外源表达会导致内源性BAF57表达减少。这种下调过程是由BAF57蛋白的蛋白酶体依赖性降解增加所介导的。此外，BAF155/170的蛋白质水平决定了BAF57在细胞中的最大量。我们绘制了负责BAF57与BAF155之间相互作用的结构域，并证明它们之间的蛋白质-蛋白质相互作用在这一调控过程中发挥着重要作用。这些发现为维持多聚酶复合体蛋白质成分适当化学计量水平的生理机制提供了见解。
