Sirtuins and Stress Response in Skin Cancer, Aging, and Barrier Function
Sirtuins (SIRT1-7) are mammalian counterparts of the yeast silent information regulator 2 (Sir2) and are a family of NAD-dependent protein deacetylases and ADP ribosyltransferases. Sirtuins regulate numerous pathways in metabolism, aging and cancer. They
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Sirtuins and Stress Response in Skin Cancer, Aging, and Barrier Function Yu-Ying He
Abstract Sirtuins (SIRT1-7) are mammalian counterparts of the yeast silent information regulator 2 (Sir2) and are a family of NAD-dependent protein deacetylases and ADP ribosyltransferases. Sirtuins regulate numerous pathways in metabolism, aging and cancer. They are critical modulators in the cellular response to metabolic, oxidative, or genotoxic stress. Recent advances have demonstrated the pivotal role of sirtuin proteins in aging and a wide range of diseases including cancer in many organs. Skin is the essential barrier protecting organisms against environmental insults and minimizing water loss from the body. New evidence in mouse models and in vitro systems has illustrated that sirtuins have important roles in skin physiology, in the barrier function, aging, and diseases such as skin cancer. This review summarizes recent advances in understanding how sirtuins regulate the skin stress response in skin cancer, aging, and barrier integrity at the molecular, cellular, and organismal levels, and in how modulating sirtuins may help prevent or treat skin cancer, skin barrier defects, and other skin diseases.
Keywords Sirtuins SIRT1 SIRT2 SIRT3 SIRT6 skin cancer Skin aging Skin barrier UV DNA repair
12.1
Introduction and Overview on Sirtuins
Sirtuins (SIRT1-7) are NAD-dependent proteins with the enzymatic activity of deacetylases and ADP ribosyltransferases (Blander and Guarente 2004; Haigis and Guarente 2006; Haigis and Sinclair 2010; Michan and Sinclair 2007; Saunders and Verdin 2007). They are mammalian counterparts of the yeast silent information regulator 2 (Sir2). Since SIRT1 was first discovered about 15 years ago, there have been major breakthroughs in understanding the critical roles of sirtuins in Y.-Y. He (&) Department of Medicine, Section of Dermatology, University of Chicago, 5841 S Maryland Ave, MC 5067, Chicago, IL 60637, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 G.T. Wondrak (ed.), Skin Stress Response Pathways, DOI 10.1007/978-3-319-43157-4_12
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Survival
DNA repair
Telomeres
Sirtuins SIRT1-7
Metabolism Stem cells
Inflammation
Differentiation
Fig. 12.1 Sirtuins regulates numerous cellular functions in stress response and homeostasis
physiology and pathology (Blander and Guarente 2004; Haigis and Guarente 2006; Haigis and Sinclair 2010; Michan and Sinclair 2007; Saunders and Verdin 2007). Sirtuins regulate a wide variety of proteins in the nucleus, cytosol and mitochondria. They are crucial regulators of tissue homeostasis and adaptation under metabolic, oxidative, or genotoxic stress. Using animal models, recent advances have demonstrated the illuminating roles of sirtuins in DNA repair, telomere integrity, metabolism, survival, inflammation, cell differentiation and stem cell biology in many human diseases including cancer and age-related diseases (Blander and Guarente 2004; Chalkiadaki and Guarente 2015; Ha
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