Tumor suppressor p53 promotes ferroptosis in oxidative stress conditions independent of modulation of ferroptosis by p21, CDKs, RB, and E2F.

ABSTRACT: p53 is a well-established critical cell cycle regulator. By inducing transcription of the gene encoding p21, p53 inhibits cyclin-dependent kinase (CDK)-mediated phosphorylation of cell cycle inhibitor retinoblastoma (RB) proteins. Phosphorylation of RB releases E2F transcription factor proteins that transactivate cell cycle-promoting genes. Here, we sought to uncover the contribution of p53, p21, CDK, RB, and E2F to the regulation of ferroptosis, an oxidative form of cell death. Our studies have uncovered unexpected complexity in this regulation. First, we showed that elevated levels of p53 enhance ferroptosis in multiple inducible and isogenic systems. On the other hand, we found that p21 suppresses ferroptosis. Elevation of CDK activity also suppressed ferroptosis under conditions where

SUBMITTER: Kuganesan N 

PROVIDER: S-EPMC8661017 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature