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

Saïd M Sebti1

  • 1Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, Florida 33612, USA. sebti@moffitt.usf.edu

Cancer Cell
|April 20, 2005
PubMed

Insights

Protein farnesylation is vital for early development and cancer progression, but not adult health. Farnesyltransferase inhibitors (FTIs) show promise, targeting Rab geranylgeranyltransferase in cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Protein farnesylation is a critical lipid modification for oncogenic proteins like Ras.
  • The precise role of protein farnesylation in normal physiology and cancer remains unclear.
  • Farnesyltransferase inhibitors (FTIs) are under clinical investigation for cancer treatment.

Purpose of the Study:

  • To elucidate the role of protein farnesylation in normal physiological processes.
  • To investigate the involvement of protein farnesylation in tumorigenesis.
  • To identify novel targets for farnesyltransferase inhibitors in cancer therapy.

Main Methods:

  • Analysis of protein farnesylation's essentiality in embryogenesis and adult homeostasis.
  • Assessment of protein farnesylation's role in tumor initiation versus progression.
  • Identification of molecular targets for farnesyltransferase inhibitors.

Main Results:

  • Protein farnesylation is essential for early embryogenesis but dispensable for adult homeostasis.
  • Farnesylation is critical for cancer progression, not initiation.
  • Rab geranylgeranyltransferase is identified as a target for certain FTIs.

Conclusions:

  • Protein farnesylation plays distinct roles in development, homeostasis, and cancer.
  • FTIs targeting Rab geranylgeranyltransferase offer potential therapeutic strategies.
  • Understanding farnesylation mechanisms is key for advancing cancer therapy.

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