A Ras-like Tumor Suppressor

Abstract

Another Ras-like tumor suppressor has been identified by Ellis et al. , adding to a growing list of heretical members of the Ras superfamily of small GTP-binding proteins. Rig (Ras-related inhibitor of cell growth) was identified through a bioinformatic search of the human expressed sequence tag database for GTP-binding proteins. It is most similar to Noey2, another Ras-like protein with tumor suppressing properties. As predicted by the Rig amino acid sequence, the protein is modified by farnesyl and geranylgeranyl isoprenoid lipids. It also inhibited Ras-mediated cell transformation when expressed in cultured cells. Rig expression is limited to human brain and heart tissue, and its loss of expression was observed in various neural tumor-derived cell lines and primary human astrocytomas. The mechanism by which loss of Rig expression causes tumorigenesis remains to be determined, although it may involve regulation of Ras effector molecules such as the kinase Raf. C. A. Ellis, M. D. Vos, H. Howell, T. Vallecorsa, D. W. Fults, G. J. Clark, Rig is a novel Ras-related protein and potential neural tumor suppressor. Proc. Natl. Acad. Sci. U.S.A. 99 , 9876-9881 (2002). [Abstract] [Full Text]