Lysine Acetylation Augments p38 Activity in Cardiomyocytes under ATP-Starved Conditions
Lysine acetylation is a key posttranslational modification that regulates the activity of target proteins. p38 is an important mediator of cellular response to stress. Pillai et al. (p. 2349–2363) provide evidence that p38 is acetylated during hypertrophy of cardiomyocytes. They mapped the acetylation to a lysine residue in the ATP-binding pocket of p38 and showed that acetylation increases affinity of p38 for ATP and thereby promotes its activity under ATP-depleted conditions like oxidative stress. The lysine residue involved in regulating p38 activity is highly conserved among other ATP-binding proteins, thus implying the possibility of a similar mechanism regulating their activity under stress conditions.
A Conserved Patch near the C Terminus of Histone H4 Is Required for Genome Stability
Although histone H4 is highly conserved during evolution, the function of its C terminus is largely unexplored. In this issue, Yao et al. (p. 2311–2325) describe the importance of three adjacent residues, L97, Y98, and G99, near the C terminus of histone H4. Mutation of any of these three residues in yeast caused slow growth, a kinetochore assembly defect, and genome instability. The observed phenotypes of the mutants are probably due to genome-wide low histone occupancy on the DNA, caused by defective histone deposition by the histone chaperones Rtt106 and CAF-I.