Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development

Mijimolle, Nieves; Velasco, Juan; Dubus, Pierre; Guerra, Carmen; Weinbaum, Carolyn A.; Casey, Patrick J.; Campuzano Uceda, María Victoria; Barbacid, Mariano

doi:http://dx.doi.org/10.1016/j.ccr.2005.03.004

Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development

Citació

Mijimolle N, Velasco J, Dubus P, Guerra C, Weinbaum CA, Casey PJ et al. Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. Cancer cell. 2005;7(4):313-24. DOI: 10.1016/j.ccr.2005.03.004

Resum

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.