Page 10 - T. Protein modification and regulation

[T. Protein modification and regulation-5]

Identification and characterization of p300-mediated

acetylated lysine residues in SERCA2a

Przemek A. Gorski², Kiyotake Ishikawa², Changwon Kho¹˙*

¹School of Korean Medicine, Pusan National University, Pusan 50612, Republic of Korea, ²Cardiovascular Research

Center, Icahn School of Medicine at Mount Sinai, New York 10029, USA.

Impaired calcium uptake resulting from reduced expression and activity of the cardiac calcium ATPase (SERCA2a) is
a hallmark of heart failure (HF). The calcium sequestering activity of SERCA2a is regulated by the phospholamban.

However, other mechanisms of SERCA2a regulation, including post-translational modifications (PTMs), have recently

emerged. Our latest analysis of SERCA2a PTMs identified lysine acetylation, which might play an important role in
regulating SERCA2a activity. Indeed, we showed that SERCA2a is acetylated and that this acetylation is more
prominent in failing human hearts. Using a cell-based screen, we found that p300 directly interacts with and

acetylates SERCA2a. Also, we showed that p300 mediated acetylation reduced SERCA2a ATPase activity. Analysis of
acetylated SERCA2a by mass spectrometry revealed lysine residues in SERCA2a susceptible to acetylation by p300.

Finally, our data demonstrate that p300 mediated acetylation of SERCA2a is a critical PTM that regulates calcium
pump function, and it may provide invaluable information necessary to develop new therapies for HF.