Pyruvate Dehydrogenase A1 Phosphorylated by Insulin Associates with Pyruvate Kinase M2 and Induces LINC00273 through Histone Acetylation.

ABSTRACT: Insulin potently promotes cell proliferation and anabolic metabolism along with a reduction in blood glucose levels. Pyruvate dehydrogenase (PDH) plays a pivotal role in glucose metabolism. Insulin increase PDH activity by attenuating phosphorylated Ser293 PDH E1α (p-PDHA1) in normal liver tissue. In contrast to normal hepatocytes, insulin enhanced p-PDHA1 level and induced proliferation of hepatocellular carcinoma HepG2 cells. Here, we attempted to find a novel function of p-PDHA1 in tumorigenesis upon insulin stimulation. We found that p-Ser293 E1α, but not the E2 or E3 subunit of pyruvate dehydrogenase complex (PDC), co-immunoprecipitated with pyruvate kinase M2 (PKM2) upon insulin. Of note, the p-PDHA1 along with PKM2 translocated to the nucleus. The p-PDHA1/PKM2 complex was associated

SUBMITTER: Hossain AJ 

PROVIDER: S-EPMC9220252 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature