Department of Molecular Biology, BK21 Graduate Program, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
Cancer Lett. 2013 Jul 28;335(2):397-403. doi: 10.1016/j.canlet.2013.02.051. Epub 2013 Mar 6.
Stress-induced premature senescence (SIPS) has been implicated in the suppression of carcinogenesis. We identified chromodomain protein 8 (CBX8), a Polycomb group (PcG) protein, as a novel binding partner of SIRT1. The interaction between CBX8 and SIRT1 was demonstrated by immunoprecipitation, GST pull-down, fluorescence microscopy, and cooperation for transcriptional repression. Like SIRT1, CBX8 repressed premature senescence and growth arrest induced by the SIRT1 inhibitor Sirtinol in MCF7 cells, which was reversed by depleting CBX8. CBX8 cooperated with SIRT1 for suppressing p53 acetylation induced by Sirtinol and etoposide/TSA. Upon ectopic expression, CBX8 or SIRT1 repressed the expression of p21(WAF1) by inhibiting p53 binding to the promoter. We provide the first evidence that CBX8 plays a potential role in regulating premature senescence in human breast cancer cells through cooperation with SIRT1.
压力诱导的过早衰老（SIPS）被认为与抑制致癌作用有关。我们鉴定了染色质域蛋白 8（CBX8），一种多梳组（PcG）蛋白，作为 SIRT1 的一个新的结合伴侣。CBX8 和 SIRT1 之间的相互作用通过免疫沉淀、GST 下拉、荧光显微镜和转录抑制的合作来证明。与 SIRT1 一样，CBX8 抑制了 MCF7 细胞中 SIRT1 抑制剂 Sirtinol 诱导的过早衰老和生长停滞，而 CBX8 的耗竭则逆转了这一作用。CBX8 与 SIRT1 合作抑制 Sirtinol 和依托泊苷/ TSA 诱导的 p53 乙酰化。在外源表达时，CBX8 或 SIRT1 通过抑制 p53 与启动子结合来抑制 p21（WAF1）的表达。我们提供了第一个证据，表明 CBX8 通过与 SIRT1 合作，在调节人类乳腺癌细胞过早衰老中发挥潜在作用。
