Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer.

ABSTRACT: Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications^1,2. Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer^3-5. High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, t

SUBMITTER: Wu D 

PROVIDER: S-EPMC6430198 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature