Sestrin2-mediated disassembly of stress granules dampens aerobic glycolysis to overcome glucose starvation.

ABSTRACT: Sestrins are a small gene family of pleiotropic factors whose actions promote cell adaptation to a range of stress conditions. In this report we disclose the selective role of Sestrin2 (SESN2) in dampening aerobic glycolysis to adapt to limiting glucose conditions. Removal of glucose from hepatocellular carcinoma (HCC) cells inhibits glycolysis associated with the downregulation of the rate-limiting glycolytic enzyme hexokinase 2 (HK2). Moreover, the accompanying upregulation of SESN2 through an NRF2/ATF4-dependent mechanism plays a direct role in HK2 regulation by destabilizing HK2 mRNA. We show SESN2 competes with insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) for binding with the 3'-UTR region of HK2 mRNA. Interactions between IGF2BP3 and HK2 mRNA result in their coalesce

SUBMITTER: Li M 

PROVIDER: S-EPMC10103035 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature