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	Sang Hyup Lee, Soo-Jong Um, Eun-Joo Kim
Journal	Cancer letters (Cancer Lett) Vol. 335 Issue 2 Pg. 397-403 (Jul 28 2013) ISSN: 1872-7980 [Electronic] Ireland
PMID	23474493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References	Antineoplastic Agents, Phytogenic Benzamides CBX8 protein, human Cyclin-Dependent Kinase Inhibitor p21 Naphthols RNA, Small Interfering Tumor Suppressor Protein p53 sirtinol Etoposide Polycomb Repressive Complex 1 SIRT1 protein, human Sirtuin 1 Sirtuins
Topics	Acetylation (drug effects) Aging, Premature Antineoplastic Agents, Phytogenic (pharmacology) Benzamides (pharmacology) Breast Neoplasms (drug therapy) Cell Line, Tumor Cellular Senescence (drug effects) Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis, drug effects) Etoposide (pharmacology) Female Humans Naphthols (pharmacology) Polycomb Repressive Complex 1 (genetics, metabolism) Promoter Regions, Genetic RNA Interference RNA, Small Interfering Sirtuin 1 (antagonists & inhibitors, metabolism) Sirtuins (antagonists & inhibitors) Tumor Suppressor Protein p53 (metabolism)

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