SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells.

Abstract	Emerging evidence suggests that Sirtuin 6 (SIRT6) functions as a longevity assurance gene by promoting genomic stability, regulating metabolic processes and attenuating inflammation. Here, we examine the effect of SIRT6 activation on cancer cells. We show that SIRT6 overexpression induces massive apoptosis in a variety of cancer cell lines but not in normal, non-transformed cells. This cell death requires the mono-ADP-ribosyltransferase but not the deacetylase activity of SIRT6 and is mediated by the activation of both the p53 and p73 apoptotic signaling cascades in cancer cells by SIRT6. These results suggest that SIRT6 is an attractive target for pharmacological activation in cancer treatment.
Authors	Michael Van Meter, Zhiyong Mao, Vera Gorbunova, Andrei Seluanov
Journal	Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 10 Issue 18 Pg. 3153-8 (Sep 15 2011) ISSN: 1551-4005 [Electronic] United States
PMID	21900744 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Culture Media DNA-Binding Proteins N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride Nuclear Proteins Phenanthrenes Poly(ADP-ribose) Polymerase Inhibitors TP53 protein, human TP73 protein, human Tumor Protein p73 Tumor Suppressor Protein p53 Tumor Suppressor Proteins ADP Ribose Transferases PARP1 protein, human Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases SIRT6 protein, human Sirtuins Glucose
Topics	ADP Ribose Transferases (genetics, metabolism) Apoptosis Cell Line, Tumor Cell Survival Culture Media (chemistry) DNA-Binding Proteins (genetics, metabolism) Gene Expression Regulation, Neoplastic Glucose (metabolism) Humans Mutagenesis, Site-Directed Nuclear Proteins (genetics, metabolism) Phenanthrenes (pharmacology) Plasmids (genetics, metabolism) Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases (metabolism) Signal Transduction Sirtuins (genetics, metabolism) Transfection Transgenes Tumor Protein p73 Tumor Suppressor Protein p53 (genetics, metabolism) Tumor Suppressor Proteins (genetics, metabolism)

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