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SJTU Research Team Found Di-Ras2 a Potential Oncogene

March 23, 2020      Author: Li Li

On February 25, 2020, the research team of Gao Weiqiang and Li Li from School of Biomedical Engineering published a paper titled “Di-Ras2 promotes renal cell carcinoma formation by activating the mitogen-activated protein kinase pathway in the absence of von Hippel–Lindau protein” in Oncogene online, a journal issued by the Nature Publishing Group addressing cancer cell genetics and the structure and function of oncogenes. In addition, the team was invited to write a review, titled “Behind the paper: Di-Ras2, a potential oncogene associated with the crosstalk between VHL-mediated ubiquitination and the MAPK pathway in ccRCC”, for Nature Research Cancer Community site.

paper

paper

The first authors of this thesis are doctoral student Rao Hanyu and doctoral student Li Xuefeng, and the corresponding author is Professor Gao Weiqiang and associate researcher Li Li. The research is sponsored by National Key Research and Development Plan by Ministry of Science and Technology, National Natural Science Foundation of China, Shanghai Science and Technology Commission and K. C. Wong Education Foundation. It is also received support from the Peak Education Plateau Construction Plan of Shanghai Education Commission.

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal human urological malignancies in the world. One of the pathological drivers for ccRCC is the Ras family of small GTPases that function as “molecular switches” in many diseases including ccRCC. Among the GTPases in the Di-Ras family, DIRAS2 gene encodes a GTPase that shares 60% homology to Ras and Rap. Yet little is known about the biological function(s) of Di-Ras2 or how its activities are regulated. In this study, we focused on Di-Ras2, and determined its functions and underlying mechanism during formation of ccRCC. We found that Di-Ras2 was upregulated in ccRCC, and promoted the proliferation, migration and invasion of human ccRCC cells in the absence of von Hippel–Lindau protein (pVHL). Mechanistically, Di-Ras2 induces and regulates ccRCC formation by modulating phosphorylation of the downstream effectors and activating the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, Di-Ras2 interacts with E3 ubiquitin ligase, pVHL, which facilitates the ubiquitination and degradation of Di-Ras2. Together, these results indicate a potential function of Di-Ras2 as an oncogene in ccRCC, and these data provide a new perspective of the relationship between pVHL and the MAPK pathway in ccRCC tumorigenesis.

Link: https://www.nature.com/articles/s41388-020-1247-y