SIRT1: tumor promoter or tumor suppressor?
Over the past decade, an intensive research on the basic biology of aging has identified individual genes either directly or indirectly involved in regulating the aging process in various model organisms. This allows us to garner all the information available from studies of model organisms and to apply them to better understand aging and cancer in human. Among many genes thus far reported contributing to aging process, the yeast silent information regulator-2 (SIR2) and its homologues in other species, which belong to the family of type III histone and protein deacetylases, have been the subject of active discussion. The demonstrated roles of SIRT1, the mammalian counterpart of the yeast SIR2, reveal that SIRT1 regulates important cellular processes including anti-apoptosis, neuronal protection, cellular senescence, aging and longevity. Based on the observations that SIRT1 is upregulated in tumor cells, the hypothesis is that deregulation of SIRT1 expression may promote tumorigenesis by altering cellular signaling or by inducing modulation of chromatin remodeling leading to promotion of tumorigenesis. Further studies will shed new light on the underlying mechanisms of tumorigenesis mediated by SIRT1.
Department of Biochemistry, Fralin Biotechnology Center, Virginia Tech, West Campus Drive, Blacksburg, VA 24061, USA. lim@vt.edu
Chang-Su
CS
Lim
D000375:Aging / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology; D006801:Humans; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics* / Q000502:physiology*; D016159:Tumor Suppressor Protein p53; D015854:Up-Regulation
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D016159:Tumor Suppressor Protein p53; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases