RB1 controls differentiation through positive regulation of phosphoglycerate mutases.

ABSTRACT: Most glycolytic enzymes are transcriptionally controlled by hypoxia-inducible factor-1α (HIF-1α) and/or MYC, however, phosphoglycerate mutases (PGAMs) are exceptional. Retinoblastoma tumor suppressor 1 (RB1) loss converts poorly spherogenic Trp53-null leiomyosarcoma cells to highly spherogenic. We determined a gene expression signature of RB1 loss-of-function in this setting and identified PGAM2 as a positive transcriptional target of RB1. Later, we found that RB1 positively controls PGAM1 as well in different tissues. RB1 deficiency induced a metabolic shift in the glycolytic pathway in a manner compatible with PGAM downregulation. Many of the metabolic features induced by RB1 loss were antagonized by PGAM overexpression. Furthermore, differentiation deficiency following RB1 loss was resc

SUBMITTER: Kohno S 

PROVIDER: S-EPMC12290115 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature