title: CBX8 suppresses Sirtinol-induced premature senescence in human breast cancer cells via cooperation with SIRT1.
abstract: 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.
authors.affiliation: Department of Molecular Biology, BK21 Graduate Program, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: Sang Hyup
authors.initials: SH
authors.lastname: Lee
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
mesh_terms: D000107:Acetylation / Q000187:drug effects; D019588:Aging, Premature; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D009284:Naphthols / Q000494:pharmacology*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037761:Sirtuins / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001549:Benzamides; C570428:CBX8 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009284:Naphthols; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C439060:sirtinol; D005047:Etoposide; D063150:Polycomb Repressive Complex 1; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins