A genome-wide genetic interaction screen reveals metabolic roles of human histone deacetylase 1

ABSTRACT: Dynamic acetylation of metabolic proteins has emerged as a ubiquitous post-translational modification of human metabolic proteins. However, the corresponding modifying enzymes and the functions of the modification await exploration. Using a genome-wide synthetic lethality screen, we constructed a genetic interaction network of human histone deacetylases (HDACs) and discovered many metabolic substrates of these enzymes. We further confirmed that the adenosine monophosphate-activated protein kinase (AMPK) catalytic subunit is acetylated and deacetylated by EP300 and HDAC1, respectively. Deacetylation of AMPK catalytic subunit enhances physical interaction with the upstream kinase LKB1, and leads to AMPK phosphorylation and activation. These findings highlight the importance of genetic intera

ORGANISM(S): Homo sapiens

SUBMITTER: Yu-yi Lin 

PROVIDER: E-GEOD-29662 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress