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Cancer Cell. 2005 Apr;7(4):297-300.

Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy.

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Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, Florida 33612, USA.


Protein farnesylation is a lipid posttranslational modification required for the cancer-causing activity of proteins such as the GTPase Ras. Although farnesyltransferase inhibitors (FTIs) are in clinical trials, their mechanism of action and the role of protein farnesylation in normal physiology are ill understood. In this issue of Cancer Cell, two articles shed light on these important issues. Protein farnesylation was found to be essential for early embryogenesis, dispensable for adult homeostasis, and critical for progression but not initiation of tumorigenesis. Furthermore, Rab geranylgeranyltransferase was identified as a target for some FTIs. This minireview discusses the implications of these findings on normal physiology, malignant transformation, and cancer therapy.

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