Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development.
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.
Mijimolle
Nieves
N
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), E-28029 Madrid, Spain.
Velasco
Juan
J
Dubus
Pierre
P
Guerra
Carmen
C
Weinbaum
Carolyn A
CA
Casey
Patrick J
PJ
Campuzano
Victoria
V
Barbacid
Mariano
M
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D020964:Embryo Loss / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D041905:Erythroid Cells / Q000201:enzymology / Q000473:pathology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D019426:Integrases / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D004965:Estrogen Antagonists; D013629:Tamoxifen; C016601:afimoxifene; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C045073:Cre recombinase; D019426:Integrases; D018631:ras Proteins