Iron regulatory protein 2 is a suppressor of mutant p53 in tumorigenesis.

ABSTRACT: p53 is known to play a role in iron homeostasis and is required for FDXR-mediated iron metabolism via iron regulatory protein 2 (IRP2). Interestingly, p53 is frequently mutated in tumors wherein iron is often accumulated, suggesting that mutant p53 may exert its gain of function by altering iron metabolism. In this study, we found that FDXR deficiency decreased mutant p53 expression along with altered iron metabolism in p53^R270H/- MEFs and cancer cells carrying mutant p53. Consistently, we found that decreased expression of mutant p53 by FDXR deficiency inhibited mutant p53-R270H to induce carcinoma and high grade pleomorphic sarcoma in FDXR^+/-; p53^R270H/- mice as compared with p53^R270H/- mice. Moreover, we found that like its effect on wild-type

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7122131 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature