The epigenetic regulator Polycomb complex protein (PcG) is thought to have a great correlation with the occurrence of various cancers. Rnf2, as the main E3 ligase in polycomb complex 1 (PRC1), has significantly increased expression levels in various tumor tissues. The relationship between Rnf2 and tumor occurrence and development has been an unsolved problem.
Using the tumor cell line and tumor tissue as a model, Zhang Jian's research team at the Institute of Genetic Development of the Chinese Academy of Sciences found that Rnf2 can promote the degradation of tumor suppressor p53 by ubiquitination. Examination of the regulatory activity of Rnf2 in a variety of cells found that Rnf2 regulates the stability of p53 only in certain cells, such as germ cell cancer. After knocking down Rnf2 in germ cell tumors cultured in vitro, obvious apoptotic cells were detected, while knocking down p53 at the same time could suppress the occurrence of apoptosis. In addition, down-regulation of Rnf2 expression can significantly inhibit tumor cell growth in vitro or in vivo. Analysis of the expression level of Rnf2 in ovarian cancer tissue microarray further showed that the high expression of Rnf2 is related to the down-regulation of p53. These results indicate that Rnf2, as a new p53 ubiquitination ligase, affects its function by regulating p53 protein stability in specific cells. This finding also suggests the possibility of Rnf2 as a cancer-specific therapeutic target.
The results of this study were published online on January 14 at PNAS (doi: 10.1073 / pnas.1211604110). Su Wenjing, a PhD student in Zhang Jian's research group, is the first author. The research was supported by the Chinese Academy of Sciences, the Ministry of Science and Technology and the National Natural Science Foundation of China.
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