Gong Lili, Govan Jeane M, Evans Elizabeth B, Dai Hui, Wang Edward, Lee Szu-Wei, Lin Hui-Kuan, Lazar Alexander J, Mills Gordon B, Lin Shiaw-Yih
a Department of Systems Biology ; The University of Texas MD Anderson Cancer Center ; Houston , TX USA.
Cell Cycle. 2015;14(14):2323-32. doi: 10.1080/15384101.2015.1044174.
The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer. Recently, PTEN has been shown to localize in the nucleus and is required to maintain genomic stability. Here, we show that nuclear PTEN, independent of its phosphatase activity, is essential for maintaining heterochromatin structure. Depletion of PTEN leads to loss of heterochromatic foci, decreased chromatin compaction, overexpression of heterochromatic genes, and reduced protein stability of heterochromatin protein 1 α. We found that the C-terminus of PTEN is required to maintain heterochromatin structure. Additionally, cancer-associated PTEN mutants lost their tumor-suppressor function when their heterochromatin structure was compromised. We propose that this novel role of PTEN accounts for its function in guarding genomic stability and suppressing tumor development.
肿瘤抑制因子PTEN是癌症中最常发生突变的基因之一。最近研究表明，PTEN定位于细胞核，对维持基因组稳定性至关重要。在此，我们发现细胞核中的PTEN，不依赖其磷酸酶活性，对于维持异染色质结构至关重要。PTEN的缺失导致异染色质位点丧失、染色质压缩减少、异染色质基因过表达以及异染色质蛋白1α的蛋白质稳定性降低。我们发现PTEN的C末端对于维持异染色质结构是必需的。此外，当异染色质结构受损时，与癌症相关的PTEN突变体失去了它们的肿瘤抑制功能。我们提出，PTEN的这一新功能解释了其在保护基因组稳定性和抑制肿瘤发展中的作用。
