As a component of the transcriptional repression complex 1 (PRC1), the ring 
finger protein RING1 participates in the epigenetic regulation in cancer. 
However, the contributions of RING1 to cancer etiology or development are 
unknown. In this study, we report that RING1 is a critical negative regulator of 
p53 homeostasis in human hepatocellular and colorectal carcinomas. RING1 acts as 
an E3 ubiquitin (Ub) ligase to directly interact with and ubiquitinate p53, 
resulting in its proteasome-dependent degradation. The RING domain of RING1 was 
required for its E3 Ub ligase activity. RING1 depletion inhibited the 
proliferation and survival of the p53 wild-type cancer cells by inducing 
cell-cycle arrest, apoptosis, and senescence, with only modest effects on 
p53-deficient cells. Its growth inhibitory effect was partially rescued by p53 
silencing, suggesting an important role for the RING1-p53 complex in human 
cancer. In clinical specimens of hepatocellular carcinoma, RING1 upregulation 
was evident in association with poor clinical outcomes. Collectively, our 
results elucidate a novel PRC1-independent function of RING1 and provide a 
mechanistic rationale for its candidacy as a new prognostic marker and/or 
therapeutic target in human cancer.Significance: These results elucidate a novel 
PRC1-independent function of RING1 and provide a mechanistic rationale for its 
candidacy as a new prognostic marker and/or therapeutic target in human cancer. 
Cancer Res; 78(2); 359-71. ©2017 AACR.