HATs and HDACs
HATs and HDACs bind to sarcomeres and regulate reversible lysine acetylation of myofilaments. HDAC inhibitors enhance contractile activity of myofilaments.
References:
Gupta MP et al. J. Biol. Chem. 283: 10135-10146, 2008.
Samant, SA et al. J. Biol. Chem. 286: 5567-77, 2011.
http://www.jbc.org/content/286/7/5567.long
Gupta MP et al. J. Biol. Chem. 283: 10135-10146, 2008.
Samant, SA et al. J. Biol. Chem. 286: 5567-77, 2011.
http://www.jbc.org/content/286/7/5567.long
PH Domain of Akt and PDK1
The PH domain of Akt and PDK1 is acetylated. This post-translational modification inhibits Akt activity. SIRT1 deacetylates and promotes Akt and PDK1 binding to PIP3 and thus activates Akt. Pro-tumorigenic and pro hypertrophic activity of Akt is regulated by SIRT1-dependent deacetylation of the kinase.
Reference:
Sundaresan NR, et al. Science Signaling 4 (182): ra46-58, 2011.
http://stke.sciencemag.org/cgi/content/full/sigtrans;4/182/ra46
Sundaresan NR, et al. Science Signaling 4 (182): ra46-58, 2011.
http://stke.sciencemag.org/cgi/content/full/sigtrans;4/182/ra46
Mitochondrial SIRT3
The mitochondrial SIRT3 protects cardiomyocytes from oxidative stress-mediated cell-death and blocks cardiac hypertrophic response by suppressing ROS synthesis from mitochondria in vivo.
References:
Sundaresan NR et al. Mol. Cell. Biol 28:6384-6401, 2008.
Sundaresan NR et al. J. Clin. Invest. 119: 2758-2771, 2009.
http://www.jci.org/articles/view/39162
Sundaresan NR et al. Mol. Cell. Biol 28:6384-6401, 2008.
Sundaresan NR et al. J. Clin. Invest. 119: 2758-2771, 2009.
http://www.jci.org/articles/view/39162
SIRT6 Deacetylase
The SIRT6 deacetylase blocks IGF-Akt signaling and development of cardiac hypertrophy by deacetylating H3K9 and preventing chromatin relaxation.
Reference:
Sundaresan NR et al. Nature Medicine. 2012
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2961.html
Sundaresan NR et al. Nature Medicine. 2012
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2961.html