PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma

ABSTRACT: Clear cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia PML protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 acti

SUBMITTER: Dr. Matilde Simoni 

PROVIDER: S-SCDT-10_1038-S44321-024-00077-3 | biostudies-other |

REPOSITORIES: biostudies-other