O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect.

ABSTRACT: The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, O-GlcNAcylation, which specifically targets Thr⁴⁰⁵ and Ser⁴⁰⁶, residues of the region encoded by the alternatively spliced exon 10 in cancer cells. We show that PKM2 O-GlcNAcylation is up-regulated in various types of human tumor cells and patient tumor tissues. The modificat

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5748163 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature