Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression.

ABSTRACT: Altering chromatin structure through histone posttranslational modifications has emerged as a key driver of transcriptional responses in cells. Modulation of these transcriptional responses by pharmacological inhibition of class I histone deacetylases (HDACs), a group of chromatin remodeling enzymes, has been successful in blocking the growth of some cancer cell types. These inhibitors also attenuate the pathogenesis of pathological cardiac remodeling by blunting and even reversing pathological hypertrophy. The mechanistic target of rapamycin (mTOR) is a critical sensor and regulator of cell growth that, as part of mTOR complex 1 (mTORC1), drives changes in protein synthesis and metabolism in both pathological and physiological hypertrophy. We demonstrated through pharmacological and genet

SUBMITTER: Morales CR 

PROVIDER: S-EPMC4836394 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature