Activated Drosophila Ras1 is selectively suppressed by isoprenyl transferase inhibitors.

Abstract:

:Ras CAAX (C = cysteine, A = aliphatic amino acid, and X = any amino acid) peptidomimetic inhibitors of farnesyl protein transferase suppress Ras-dependent cell transformation by preventing farnesylation of the Ras oncoprotein. These compounds are potential anticancer agents for tumors associated with Ras mutations. The peptidomimetic FTI-254 was tested for Ras1-inhibiting activity in whole animals by injection of activated Ras1val12 Drosophila larvae. FTI-254 decreased the ability of Ras1val12 to form supernumerary R7 photoreceptor cells in the compound eye of transformed flies. In contrast, it had no effect on the related supernumerary R7 phenotypes of flies transformed with either the activated sevenless receptor tyrosine kinase, Raf kinase, or a chimeric Ras1val12 protein that is membrane associated through myristylation instead of isoprenylation. Therefore, FTI-254 acts as an isoprenylation inhibitor to selectively inhibit Ras1val12 signaling activity in a whole-animal model system.

authors

Kauffmann RC,Qian Y,Vogt A,Sebti SM,Hamilton AD,Carthew RW

doi

10.1073/pnas.92.24.10919

subject

Has Abstract

pub_date

1995-11-21 00:00:00

pages

10919-23

issue

24

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

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