Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development

Abstract

Protein farnesyltransferase (FTase) is an enzyme responsible for posttranslational modification of proteins carrying a carboxy-terminal CaaX motif. Farnesylation allows substrates to interact with membranes and protein targets. Using gene-targeted mice, we report that FTase is essential for embryonic development, but dispensable for adult homeostasis. Six-month-old FTase-deficient mice display delayed wound healing and maturation defects in erythroid cells. Embryonic fibroblasts lacking FTase have a flat morphology and reduced motility and proliferation rates. Ablation of FTase in two ras oncogene-dependent tumor models has no significant consequences for tumor initiation. However, elimination of FTase during tumor progression had a limited but significant inhibitory effect. These results should help to better understand the role of protein farnesylation in normal tissues and in tumor development.This work was supported by grants from the V Framework Programme of the European Union (QLK3-1999-00875) to M.B. and from the Ministerio de Ciencia y Tecnologia (SAF2001-0058) and Fondo de Investigación Sanitaria (00/0109) to J.V. P.D. was supported by the Association pour la Recherche contre le Cancer (ARC). P.J.C. was supported by NIH grant GM46372. N.M. was supported by a BEFI Fellowship from the Fondo de Investigación Sanitaria. The CNIO is partially supported by the RTICCC (Red de Centros de Cáncer; FIS C03/10