Cancer cells typically manifest unrestricted proliferation and metastasis. One way the cancer cells acquire malignant traits is through the loss of function of tumor suppressor genes, genes that keep the cells from aberrant behaviors. A group led by Professor Gong Yaoqin at School of Medicine of Shandong University now reported a new cancer-promoting player in the silencing of tumor suppressors.

Their findings were reported in the December 2012 issue of Cancer Cell, the top journal in the field of cancer research. The paper, entitled “CRL4B Catalyzes H2AK119 Monoubiquitination and Coordinates with PRC2 to Promote Tumorigenesis”, listed graduate student Hu Huili as the first author, and Prof. Gong Yaoqin and Prof. Wang Yan as the co-corresponding authors.

They found that in many types of cancer, the protein, called CUL4B for culling 4B, is highly expressed and positively correlated with the tumor grade. They further showed that CUL4B promotes tumor formation and progression by repressing the expression of key tumor suppressors such as p16 and PTEN. A CUL4B-DDB1-Roc1 (CRL4B) complex coordinate with another well-known repressor complex called PRC2 in promoting H3K27me trimethylation and H2AK119 monoubiquitination, which are key histone modifying steps in turning off gene expression. Their work illustrated a novel crosstalk between different types of histone modification. Because CUL4B acts as a cancer-promoting gene, it has the potential to be a cancer therapy target.

The CUL4B is not new to Dr. Gong’s research group. Back in 2007, they discovered that that a loss of function mutation in CUL4B causes a mental retardation syndrome in males and that the cells without CUL4B function were at a great disadvantage when compared to CUL4B functional cells in females. Thus, CUL4B plays a critical role in normal development, but when it is produced too much, it results in the formation of cancer. The research conducted in Dr. Gong’s group has been supported by grants from the National Nature Science Fund and Ministry of Science and Technology of China.

Written by: Liu Qiji

Edited by: Lawrence Phillips, Jing Zizhao

Source: School of Medicine,www.view.sdu.edu.cn