The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy

Science Signaling

Volumn 4, Issue 182, 2011, Pages

  Sundaresan, Nagalingam R ^a   Pillai, Vinodkumar B ^a   Wolfgeher, Don ^a   Samant, Sadhana ^a   Vasudevan, Prabhakaran ^a   Parekh, Vishwas ^a   Raghuraman, Hariharasundaram ^a   Cunningham, John M ^a   Gupta, Madhu ^b   Gupta, Mahesh P ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN II; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PROTEIN KINASE B; SIRTUIN 1; PHOSPHATIDYLINOSITOL 3,4,5-TRIPHOSPHATE; POLYPHOSPHOINOSITIDE; PROTEIN SERINE THREONINE KINASE; PYRUVATE DEHYDROGENASE (ACETYL TRANSFERRING) KINASE; PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING) KINASE; SIRT1 PROTEIN, HUMAN; SIRT1 PROTEIN, MOUSE;

ACETYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CONTROLLED STUDY; DEACETYLATION; ENZYME ACTIVATION; ENZYME LOCALIZATION; ENZYME PHOSPHORYLATION; EXERCISE; HEART; HEART VENTRICLE HYPERTROPHY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ANIMAL; CARDIOMEGALY; CELL MEMBRANE; CELL STRAIN HEK293; CELL TRANSFORMATION; GENETICS; HELA CELL; METABOLISM; MOUSE MUTANT; MUTATION; PATHOLOGY; PHOSPHORYLATION;

MUS;

ACETYLATION; ANIMALS; CARDIOMEGALY; CELL MEMBRANE; CELL TRANSFORMATION, NEOPLASTIC; ENZYME ACTIVATION; HEK293 CELLS; HELA CELLS; HUMANS; MICE; MICE, KNOCKOUT; MUTATION; PHOSPHATIDYLINOSITOL PHOSPHATES; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIRTUIN 1;

EID: 79960620082     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001465     Document Type: Article

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55. Acknowledgments: We thank B.-C. He for his technical help in injecting cells in nude mice. We are also grateful to W. McBurney (University of Ottawa, Canada) for providing SIRT1-KO mice. Adenovirus vectors synthesizing shRNA against p300 and SIRT1 were provided by B. Thimmapaya (Northwestern University, Chicago, IL) and P. Puigserver (Harvard Medical School, Boston, MA), respectively. Funding: This study was supported by NIH grants RO1 HL-77788 and HL-83423 to M.P.G. N.R.S. was supported by a postdoctoral fellowship grant from the American Heart Association. Author contributions: Most of the experiments in this study were done by N.R.S. V.B.P. performed time course and cellular NAD/NADH ratio experiments. J.M.C. was involved in the planning of experiments related to cancer growth. D.W. did MS/MS analysis. S.S. was involved in creating Akt mutants and performed GST pull-down assays and localization experiments. P.V. and V.P. worked in the laboratory of J.M.C. and did experiments related to cancer cell growth and tumorigenesis. H.R. generated in silico models showing interaction of the PH domain of Akt and PDK1 with PIP3. M.G. analyzed cardiac hypertrophy in mice. M.P.G. coordinated with different investigators and prepared the manuscript. Competing interests: The authors declare that they have no competing interests. Data availability: The MS data associated with this manuscript may be downloaded from the Proteome Commons Tranche repository at https:// proteomecommons.org/tranche/ (Tranche hash: Ar624VS4wP/z/ 2MG7dPnqkgNsh0iEiT/ 3943A7xZPQcseJLI+2oV1fsnC7Ti0sqKiWK8l3b2E86cdwPfw6BgPQ2Tc+EAAAAAAAACFQ==).