Title:
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Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development
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Author:
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Mijimolle, Nieves; Velasco, Juan; Dubus, Pierre; Guerra, Carmen; Weinbaum, Carolyn A.; Casey, Patrick J.; Campuzano Uceda, María Victoria; Barbacid, Mariano
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Abstract:
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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. |
Abstract:
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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) |
Subject(s):
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-Homeòstasi -Tumors |
Rights:
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© Elsevier. This is the published version of an article http://dx.doi.org/10.1016/j.ccr.2005.03.004 that appeared in the journal Cancer cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-license |
Document type:
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Article Article - Published version |
Published by:
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Elsevier
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