Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 19 July 2011
Vol. 4, Issue 182, p. ra46
[DOI: 10.1126/scisignal.2001465]


Editor's Summary

Deacetylation for Activation
Cell growth can be physiological (such as when heart cells expand in size in response to exercise, a process called cardiac hypertrophy) or pathological (such as in cancer) and is promoted by the kinase Akt. Sundaresan et al. showed that acetylation blocked the activity of Akt and its activating kinase PDK1 by interfering with the lipid-binding sites of these proteins, whereas deacetylation enhanced their activities. Mice injected with cells containing a mutant Akt that mimicked acetylated Akt formed smaller tumors, and the extent of cardiac hypertrophy was decreased in mice that lacked SIRT1, the protein that deacetylated Akt. These results provide insight into understanding the mechanisms that regulate the activity of Akt and may enable the development of new ways to promote or inhibit cell growth.

Citation: N. R. Sundaresan, V. B. Pillai, D. Wolfgeher, S. Samant, P. Vasudevan, V. Parekh, H. Raghuraman, J. M. Cunningham, M. Gupta, M. P. Gupta, The Deacetylase SIRT1 Promotes Membrane Localization and Activation of Akt and PDK1 During Tumorigenesis and Cardiac Hypertrophy. Sci. Signal. 4, ra46 (2011).

Read the Full Text

Sirt2 Deacetylase Is a Novel AKT Binding Partner Critical for AKT Activation by Insulin.
G. Ramakrishnan, G. Davaakhuu, L. Kaplun, W.-C. Chung, A. Rana, A. Atfi, L. Miele, and G. Tzivion (2014)
J. Biol. Chem. 289, 6054-6066
   Abstract »    Full Text »    PDF »
Regulation of Akt Signaling by Sirtuins: Its Implication in Cardiac Hypertrophy and Aging.
V. B. Pillai, N. R. Sundaresan, and M. P. Gupta (2014)
Circ. Res. 114, 368-378
   Abstract »    Full Text »    PDF »
SIRT1 Protein, by Blocking the Activities of Transcription Factors FoxO1 and FoxO3, Inhibits Muscle Atrophy and Promotes Muscle Growth.
D. Lee and A. L. Goldberg (2013)
J. Biol. Chem. 288, 30515-30526
   Abstract »    Full Text »    PDF »
Akt SUMOylation Regulates Cell Proliferation and Tumorigenesis.
R. Li, J. Wei, C. Jiang, D. Liu, L. Deng, K. Zhang, and P. Wang (2013)
Cancer Res. 73, 5742-5753
   Abstract »    Full Text »    PDF »
A Cardiac-enriched MicroRNA, miR-378, Blocks Cardiac Hypertrophy by Targeting Ras Signaling.
R. S. Nagalingam, N. R. Sundaresan, M. P. Gupta, D. L. Geenen, R. J. Solaro, and M. Gupta (2013)
J. Biol. Chem. 288, 11216-11232
   Abstract »    Full Text »    PDF »
ANG II causes insulin resistance and induces cardiac metabolic switch and inefficiency: a critical role of PDK4.
J. Mori, O. A. Alrob, C. S. Wagg, R. A. Harris, G. D. Lopaschuk, and G. Y. Oudit (2013)
Am J Physiol Heart Circ Physiol 304, H1103-H1113
   Abstract »    Full Text »    PDF »
Sirt1 inhibits the transcription factor CREB to regulate pituitary growth hormone synthesis.
J. Monteserin-Garcia, O. Al-Massadi, L. M. Seoane, C. V. Alvarez, B. Shan, J. Stalla, M. Paez-Pereda, F. F. Casanueva, G. K. Stalla, and M. Theodoropoulou (2013)
FASEB J 27, 1561-1571
   Abstract »    Full Text »    PDF »
SIRT1 is a Highly Networked Protein That Mediates the Adaptation to Chronic Physiological Stress.
M. W. McBurney, K. V. Clark-Knowles, A. Z. Caron, and D. A. Gray (2013)
Genes & Cancer 4, 125-134
   Abstract »    Full Text »    PDF »
From Sirtuin Biology to Human Diseases: An Update.
C. Sebastian, F. K. Satterstrom, M. C. Haigis, and R. Mostoslavsky (2012)
J. Biol. Chem. 287, 42444-42452
   Abstract »    Full Text »    PDF »
The Intersection Between Aging and Cardiovascular Disease.
B. J. North and D. A. Sinclair (2012)
Circ. Res. 110, 1097-1108
   Abstract »    Full Text »    PDF »
Growth Factors, Nutrient Signaling, and Cardiovascular Aging.
L. Fontana, M. Vinciguerra, and V. D. Longo (2012)
Circ. Res. 110, 1139-1150
   Abstract »    Full Text »    PDF »
SIRT1-mediated acute cardioprotection.
S. M. Nadtochiy, H. Yao, M. W. McBurney, W. Gu, L. Guarente, I. Rahman, and P. S. Brookes (2011)
Am J Physiol Heart Circ Physiol 301, H1506-H1512
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882