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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.