Cell Signaling

Akt Acetylation

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Science  05 Aug 2011:
Vol. 333, Issue 6043, pp. 675
DOI: 10.1126/science.333.6043.675-c

The protein kinase Akt is activated in response to growth factors and is implicated in diseases such as cancer and cardiac hypertrophy. Inhibition of Akt has been associated with extended life span. Activity of Akt thus requires tight control, as evidenced by the multiple means by which Akt is regulated: phosphorylation, ubiquitination, and binding to phospholipids. Sundaresan et al. add another layer of regulation to the mix: reversible acetylation. Akt was acetylated in mouse cells in a manner inversely related to its activation. The kinase was associated with the histone deactylase SIRT1, and deacetylation enhanced its ability to be activated. In contrast, activation of Akt in response to a growth factor was inhibited in cells lacking SIRT1. Cells expressing a mutant form of Akt designed to act as though it was always acetylated, formed smaller tumors in a mouse model. Effects on cardiac hypertrophy in mice lacking or overexpressing SIRT1 were associated with altered regulation of Akt. Thus, acetylation of Akt, as regulated by SIRT1, appears to be an important aspect of control of diverse biological activities of the enzyme.

Sci. Sig. 4, ra46 (2011).

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