The Deubiquitylase OTUB1 Mediates Ferroptosis via Stabilization of SLC7A11

Abstract Although cell-cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, nonapoptotic form of cell death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as…

• NI
  National Institutes of Health

  Award: 5RO1CA190477, 5RO1CA085533, 5RO1CA216884, and 5RO1CA224272
• NC
  National Cancer Institute