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Abstract Diverse functions of SIRT1 regulated by DBC1 in cancer Ja-Eun Kim Department of Pharmacology, Kyung Hee University, School of Medicine SIRT1, a protein deacetylase, participates in various cellular functions including gene silencing, cell proliferation, apoptosis, metabolism and tumorigenesis. Whereas the cellular functions of SIRT1 have been extensively investigated, less is known about the regulation of SIRT1 activity. Here we show that Deleted in Breast Cancer-1 (DBC1) directly interacts and inhibits SIRT1 deacetylase activity in vitro and in vivo. Downregulation of DBC1 expression enhances the deacetylation of SIRT1-target proteins such as p53 and FOXO, and thus potentiates SIRT1-dependent inhibition of apoptosis induced by cellular stress, suggesting a possible role of DBC1 as a tumor suppressor. In addition, we have shown the novel function of SIRT1 to guard the genomic integrity although SIRT1 deacetylation target has not been identified in this pathway. In this context, DBC1 localized in chromatin inhibits the SIRT1-dependent repair and plays a role as a possible tumor promoter. Overall, DBC1 exerts opposite functions in the regulation of tumorigenesis by inhibiting the deacetylase activity of SIRT1. Therefore, the interface between DBC1 and SIRT1 would be a potential therapeutic target of cancer.