Regulating SWI/SNF subunit levels via protein-protein interactions and proteasomal degradation: BAF155 and BAF170 limit expression of BAF57
Regulating SWI/SNF subunit levels via protein-protein interactions and proteasomal degradation: BAF155 and BAF170 limit expression of BAF57
复制标题
DOI：
10.1128/mcb.25.20.9016-9027.2005
复制
发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Archer, TK
中科院分区：
文献类型：
--
作者：
Chen, JG;Archer, TK
哺乳动物的SWI/SNF染色质重塑复合物，其功能是至关重要的转录调控，包含约10个蛋白质组分。核心SAI/SNF亚基（包括BRG 1/Brm、BAF 155、BAF 170、BAF 60、hSNF/BRM 1和BAF 57）的表达水平是化学计量的，细胞中几乎没有未结合的分子。在这里，我们报告说，外源性表达的野生型或某些缺失突变体的BAF 57，一个关键的亚基，介导的重塑复合物和转录因子之间的相互作用，导致内源性BAF 57的表达减少。该下调过程由BAF 57蛋白的蛋白酶体依赖性降解的增加介导。此外，BAF 155/170的蛋白质水平决定了BAF 57的最大细胞量。我们绘制了负责BAF 57和BAF 155之间相互作用的结构域，并证明了它们之间的蛋白质-蛋白质相互作用在这一调控过程中起着重要作用。这些发现提供了对负责维持包含多聚体酶复合物的蛋白质组分的适当化学计量水平的生理机制的见解。
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 SAI/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.