Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer.

ABSTRACT: Coordination of gene expression with nutrient availability supports proliferation and homeostasis and is shaped by protein acetylation. Yet how physiological/pathological signals link acetylation to specific gene expression programs and whether such responses are cell-type-specific is unclear. AMP-activated protein kinase (AMPK) is a key energy sensor, activated by glucose limitation to resolve nutrient supply-demand imbalances, critical for diabetes and cancer. Unexpectedly, we show here that, in gastrointestinal cancer cells, glucose activates AMPK to selectively induce EP300, but not CREB-binding protein (CBP). Consequently, EP300 is redirected away from nuclear receptors that promote differentiation towards β-catenin, a driver of proliferation and colorectal tumorigenesis. Importantly,

SUBMITTER: Gutierrez-Salmeron M 

PROVIDER: S-EPMC7326158 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature