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, SIRTI 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, SIRTI 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 SIRTI which may provide the basis for the development of therapeutic inhibitors with improved specificity. (C) 2008 Elsevier Inc. All rights reserved.