Chromatin and beyond: the multitasking roles for SIRT6.
In recent years there has been a large expansion in our understanding of SIRT6 biology including its structure, regulation, biochemical activity, and biological roles. SIRT6 functions as an ADP-ribosylase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty-acyl groups. Through these functions SIRT6 impacts upon cellular homeostasis by regulating DNA repair, telomere maintenance, and glucose and lipid metabolism, thus affecting diseases such diabetes, obesity, heart disease, and cancer. Such roles may contribute to the overall longevity and health of the organism. Until recently, the known functions of SIRT6 were largely restricted to the chromatin. In this article we seek to describe and expand this knowledge with recent advances in understanding the mechanisms of SIRT6 action and their implications for human biology and disease.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Sita
S
Kugel
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: rmostoslavsky@mgh.harvard.edu.
Raul
R
Mostoslavsky
D000818:Animals; D002843:Chromatin / Q000201:enzymology / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D003920:Diabetes Mellitus / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006331:Heart Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008136:Longevity / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis
D002843:Chromatin; C516592:SIRT6 protein, human; D037761:Sirtuins; D005947:Glucose
DNA repair; aging and inflammation; cancer; histone deacetylase; metabolism; sirtuin 6