The Deacetylase SIRT1 Promotes Membrane Localization and Activation of Akt and PDK1 During Tumorigenesis and Cardiac Hypertrophy

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

*To whom correspondence should be addressed. E-mail: mgupta{at}surgery.bsd.uchicago.edu

This PDF file includes:

• Fig. S1. Akt is acetylated at Lys¹⁴ and Lys²⁰ in the PH domain.
• Fig. S2. SIRT1 binds to Akt under growth-promoting conditions.
• Fig. S3. SIRT1 binds to the PH domain of Akt.
• Fig. S4. SIRT1 deacetylates and activates Akt in cells.
• Fig. S5. SIRT1-depleted cells show increased FOXO transcriptional activity.
• Fig. S6. SIRT1 overexpression rescues phosphorylation of Akt in SIRT1-KO cells.
• Fig. S7. Growth factor treatment of cells increases the NAD/NADH ratio.
• Fig. S8. Acetylation specifically alters the binding ability of Akt to PIP₃.
• Fig. S9. The PH domain of PDK1 is acetylated at Lys⁴⁹⁵ and Lys⁵³⁴.
• Fig. S10. SIRT1 localizes to the plasma membrane under growth-promoting conditions.
• Fig. S11. SIRT1-deficient PC3 cells do not show IGF-1–induced phosphorylation of PDK1.
• Fig. S12. SIRT1-deficient PC3 cells show reduced activation of Akt.
• Fig. S13. Lys²⁰ acetylation inhibits the tumorigenic activity of Akt.
• Fig. S14. SIRT1^−/− mice show reduced AngII-mediated cardiac hypertrophy.
• Fig. S15. SIRT1^−/− mouse liver shows reduced Akt phosphorylation.
• Fig. S16. AngII infusion fails to induce hypertrophic markers in SIRT1^−/− mice.
• Fig. S17. SIRT1 deficiency blocks the development of physiologic hypertrophy.
• Fig. S18. The Akt inhibitor triciribine blocks SIRT1-mediated hypertrophy of cardiomyocytes.
• Table S1. Relative stoichiometry of acetylation of the PH domain of Akt.
  

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© 2011 American Association for the Advancement of Science