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Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins.
Kang, Hyeog; Oka, Shinichi; Lee, Duck-Yeon; Park, Junhong; Aponte, Angel M; Jung, Young-Sang; Bitterman, Jacob; Zhai, Peiyong; He, Yi; Kooshapur, Hamed; Ghirlando, Rodolfo; Tjandra, Nico; Lee, Sean B; Kim, Myung K; Sadoshima, Junichi; Chung, Jay H.
Afiliación
  • Kang H; Laboratory of Obesity and Aging Research, Genetics and Development Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Oka S; Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey 07101, USA.
  • Lee DY; Biochemistry Core Facility, Biochemistry and Biophysics Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Park J; Tulane University School of Medicine, Department of Pathology, New Orleans, Louisiana 70112, USA.
  • Aponte AM; Proteomics Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Jung YS; Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 120-140, Republic of Korea.
  • Bitterman J; Laboratory of Obesity and Aging Research, Genetics and Development Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Zhai P; Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey 07101, USA.
  • He Y; Laboratory of Molecular Biophysics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Kooshapur H; Laboratory of Molecular Biophysics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Ghirlando R; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Tjandra N; Laboratory of Molecular Biophysics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Lee SB; Tulane University School of Medicine, Department of Pathology, New Orleans, Louisiana 70112, USA.
  • Kim MK; Laboratory of Obesity and Aging Research, Genetics and Development Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Sadoshima J; Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers University, New Jersey Medical School, Newark, New Jersey 07101, USA.
  • Chung JH; Laboratory of Obesity and Aging Research, Genetics and Development Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Commun ; 8: 15560, 2017 05 15.
Article en En | MEDLINE | ID: mdl-28504272
Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1's ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenosina Trifosfato / Sirtuina 1 Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenosina Trifosfato / Sirtuina 1 Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos