One paper, by Dr. Lorena Beese, Dr. Patrick Casey, and colleagues at Duke University, reports the detailed, three-dimensional structure of the rat enzyme farnesyltransferase (FTase), which shares 97% sequence identity with the human enzyme. Human FTase is considered a promising anticancer drug target by several pharmaceutical companies. The enzyme activates a protein known as Ras that is essential for life, but which in a mutant form is associated with up to a quarter of all cancers. Inhibition of FTase has been shown to shrink or eliminate Ras-induced cancers in mice without causing significant side effects. The reported structure, determined by x-ray crystallography, reveals details of FTase that may aid efforts to design human chemotherapy agents targeting the enzyme.
The second paper describes work by Dr. Jasper Rine and graduate student Victor Boyartchuk at the University of California, Berkeley, together with Dr. Matthew Ashby of Acacia Biosciences Incorporated in Richmond, CA. Working with yeast (a model organism that frequently reveals insights about human systems), the researchers report the discovery of two enzymes involved in chemically grooming proteins for their final function. One of the enzymes, called Rce1 protein, is necessary to activate Ras proteins. Inhibition of Rce1 protein appears to reduce but not eliminate Ras function, suggesting that a drug targeting Rce1 protein might be an effective chemotherapy agent.
The work reported in both papers was partially supported by the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health that supports basic biomedical research.
Boyartchuk VL, Ashby MN, Rine J. Modulation of Ras and a-Factor Function by Carboxyl-Terminal Proteolysis. Ibid., p. 1796-1800.
Gelb M. Protein Prenylation, et cetera: Signal Transduction in Two Dimensions. Ibid., p. 1750-51.