Nagalingam R Sundaresan, Prabhakaran Vasudevan, Lei Zhong, Gene Kim, Sadhana Samant, Vishwas Parekh, Vinodkumar B Pillai, P V Ravindra, Madhu Gupta, Valluvan Jeevanandam, John M Cunningham, Chu-Xia Deng, David B Lombard, Raul Mostoslavsky, Mahesh P Gupta
Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy...
November 2012: Nature Medicine