SIRTUIN 1: regulating the regulator.
Earlier analyses on the sirtuin family of histone deacetylases and its well-known member SIRT1 had their primary focus mostly on the identification of cellular targets exploring molecular mechanisms and functional networks in the control of metabolic homeostasis, differentiation, apoptosis and cell survival. However, only little is known about the regulation of SIRT1 itself, so far. Presently, SIRT1 is gaining increasing importance in the development of innovative treatment strategies for cancer, neurodegenerative disorders and metabolic disease. Based on differences in their catalytic activities, SIRT1 and the sirtuins in general, are insensitive to the classical class I and II HDAC inhibitors which are increasingly becoming part of treatment regimens for solid tumors and hematological malignancies. In this review we outline recent research advances on the regulation of SIRT1 which may provide the basis for the development of therapeutic inhibitors with improved specificity.
Zschoernig
Barbara
B
Saarland University Medical Center, Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Center for Immunotherapy and Gene Therapy, Kirrberger Strasse, Building 40, D-66421 Homburg/Saar, Germany.
Mahlknecht
Ulrich
U
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases