例如:"lncRNA", "apoptosis", "WRKY"

The E3 Ligase RING1 Targets p53 for Degradation and Promotes Cancer Cell Proliferation and Survival.

Cancer Res.2018 Jan 15;78(2):359-371. Epub 2017 Nov 29
Jiajia Shen 1 , Pengyu Li 2 , Xuejing Shao 3 , Yang Yang 4 , Xiujun Liu 1 , Min Feng 5 , Qiang Yu 5 , Ronggui Hu 6 , Zhen Wang 7
Jiajia Shen 1 , Pengyu Li 2 , Xuejing Shao 3 , Yang Yang 4 , Xiujun Liu 1 , Min Feng 5 , Qiang Yu 5 , Ronggui Hu 6 , Zhen Wang 7
+ et al

[No authors listed]

Author information
  • 1 Department of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 Qilu Hospital of Shandong University, Jinan, China.
  • 3 Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
  • 4 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
  • 5 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Biopolis, Singapore.
  • 6 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. wangzhen@imb.pumc.edu.cn coryhu@sibcb.ac.cn.
  • 7 Department of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. wangzhen@imb.pumc.edu.cn coryhu@sibcb.ac.cn.

摘要


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.