New job for an old tool: PI3Kβ phosphorylates OGT to regulate acetyl-CoA in glioblastoma

Abstract

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PI3Kβ) is recognized for its role in cellular signaling as a lipid kinase. He and colleagues recently reported a non-canonical function of PI3Kβ where, under high glucose, it phosphorylates and activates O-GlcNAc transferase (OGT). This activation enhances ATP-citrate synthase (ACLY) O-GlcNAcylation, increasing acetyl-CoA production, fueling fatty acid metabolism and histone acetylation, and driving glioblastoma (GBM) growth.