<i>SOD1</i> is a synthetic-lethal target in <i>PPM1D</i>-mutant leukemia cells.

ABSTRACT: The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg²⁺/Mn²⁺-dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our results demonstrate a r

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11186636 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature