Protein ubiquitination regulates multiple cancer-related cellular processes, including cell cycle. Typically, it is sequentially mediated by three enzymes: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3) that controls substrate specificity. During which, ubiquitin E3 ligases are considered to be the next wave of molecules for targeted therapy. However, the function of numerous E3 ligases still remains unclear.

Recently, Dr. CHEN Ceshi’s research team (Kunming Institute of Zoology, the Chinese Academy of Sciences) have identified a novel E3 ligase, RING finger protein 126 (RNF126), by screening a functional small interfering RNA library containing siRNA pools against 555 E3 ligases. Their results indicate that the depletion of RNF126 suppresses breast and prostate cancer cell growth by inducing G1/S cell cycle arrest. The protein array analysis suggests that the cell cycle-dependent kinase inhibitor p21 is a substrate of RNF126 E3 ligase. RNF126 ubiquitinates and accelerates the degradation of p21 protein, meanwhile, p21 protein has high significance in cell cycle and proliferation. So, as the consequence, either the cell cycle progression or cancer cells growth from breast and prostate have been promoted both in vitro and in vivo.

The main findings of this study have been published on Cell Research (http://cancerres.aacrjournals.org/content/early/2012/09/28/0008-5472.CAN-12-0562.abstract), and it has for the first time narrated the full story of the function and mechanisms of RNF 126, indicating the potential role RNF 126 as a cancer therapeutic target. The high originality of this study also indicates its strong application potentials, such as for the early diagnosis and outcome prediction of breast and prostate cancer.

This study was supported by National Nature Science Foundation of China , Top Talents Program of Yunnan Province, China, and Strategic Priority Research Program of the Chinese Academy of Sciences，Stem Cell and Regenerative Medicine Research.