The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity

ABSTRACT: Although iron is required for cell proliferation, iron-dependent programmed cell death serves as a critical barrier to tumor growth and metastasis. Emerging evidence suggests that iron-mediated lipid oxidation also facilitates immune eradication of cancer. However, the regulatory mechanisms of iron metabolism in cancer remain unclear. Here we identify OTUD1 as the deubiquitinase of Iron-responsive element-binding protein 2 (IREB2), selectively reduced in colorectal cancer. Clinically, downregulation of OTUD1 is highly correlated with poor outcome of cancer. Mechanistically, OTUD1 promotes Transferrin receptor protein 1 (TFRC)-mediated iron transportation through deubiquitinating and stabilizing IREB2, leading to increased ROS generation and ferroptosis. Moreover, presence of OTUD1 promotes

SUBMITTER: Jia Song 

PROVIDER: S-SCDT-EMBOR-2020-51162V1P | biostudies-other |

REPOSITORIES: biostudies-other