Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells.

ABSTRACT: The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB's role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-speci

SUBMITTER: Varaljai R 

PROVIDER: S-EPMC4573855 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature