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Sci. STKE, 23 March 2004
Vol. 2004, Issue 225, p. pe13
[DOI: 10.1126/stke.2252004pe13]

PERSPECTIVES

Methotrexate and Ras Methylation: A New Trick for an Old Drug?

Mark R. Philips

Departments of Medicine, Cell Biology, and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Abstract: Ras plays a central role in the development and progression of human cancer. Ras function depends on its ability to associate with cellular membranes. Nascent Ras is targeted to membranes by virtue of a series of posttranslational modifications of a C-terminal "CAAX" motif that include farnesylation, proteolysis, and carboxyl methylation. This pathway is an attractive target for anti-Ras drug development. Farnesyltransferase inhibitors have been developed and are in clinical trials. Their success has prompted interest in developing pharmacologically useful inhibitors of the other two enzymes in the Ras processing pathway. Ironically, it now appears that methotrexate, one of the oldest chemotherapeutic drugs, may work, in part, by inhibiting carboxyl methylation of Ras.

*Contact information. Telephone, 212-263-7404; fax, 212-263-3707; e-mail, philim01{at}med.nyu.edu

Citation: M. R. Philips, Methotrexate and Ras Methylation: A New Trick for an Old Drug? Sci. STKE 2004, pe13 (2004).

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