Promoter demethylation of the asparagine synthetase gene is required for ATF4-dependent adaptation to asparagine depletion.

ABSTRACT: Tumor cells adapt to nutrient-limited environments by inducing gene expression that ensures adequate nutrients to sustain metabolic demands. For example, during amino acid limitations, ATF4 in the amino acid response induces expression of asparagine synthetase (ASNS), which provides for asparagine biosynthesis. Acute lymphoblastic leukemia (ALL) cells are sensitive to asparagine depletion, and administration of the asparagine depletion enzyme l-asparaginase is an important therapy option. ASNS expression can counterbalance l-asparaginase treatment by mitigating nutrient stress. Therefore, understanding the mechanisms regulating ASNS expression is important to define the adaptive processes underlying tumor progression and treatment. Here we show that DNA hypermethylation at the AS

SUBMITTER: Jiang J 

PROVIDER: S-EPMC6901317 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature