PBRM1与核纤层成分互作及其在肾癌细胞中的作用和分子机理

透明肾细胞癌(ccRCC)是肾癌中最常见的肿瘤，染色质重塑复合体PBAF的特异亚基基因PBRM1在其中的失活突变率达41%, 而核纤层蛋白基因 LMNA/LMNB1/LMNB2在ccRCC病人样品中的拷贝数变异可达到13.8%。抑癌基因PBRM1与核纤层蛋白基因的改变合计可出现在近50%的ccRCC病例中，表明PBRM1和核纤层在ccRCC中有着重要作用。而我们的蛋白质组学研究表明PBRM1蛋白和细胞核纤层蛋白间的确存在者相互作用。本项目拟以PBRM1和LaminA、LaminB1为主要研究对象，探讨其蛋白产物之间的互作，及其对基因组结构、功能、细胞代谢的影响，有望揭示肿瘤抑制基因PBRM1、核纤层在ccRCC中的重要生物学功能及新的分子机制。

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). The mutation rate of PBRM1 (a subunit of PBAF chromatin remodeling complex) is 41% in ccRCC. The copy number variation of LMNA/LMNB1/LMNB2 genes in clinic ccRCC samples was 13.8%. Together these alterations can be found in nearly 50% of ccRCC cases, indicating that PBRM1 and nulclear lamina play an important role in ccRCC. More over, our proteomic data demonstrates the interaction between PBRM1 and nuclear lamina proteins. This project is intended to investigate the role of PBRM1, LaminA and LaminB1, as well as the interaction between them.We will also explore their effects on the structure and function of the genome,metabolism， and the roles that PBRM1 and nuclear lamina are playing in ccRCC, as well as the underlying molecular mechanisms.