Therapeutic intervention based on protein prenylation and associated modifications

Michael H. Gelb, Lucas Brunsveld, Christine A. Hrycyna, Susan Michaelis, Fuyuhiko Tamanoi, Wesley C. Van Voorhis, Herbert Waldmann

Research output: Contribution to journalReview articlepeer-review

Abstract

In eukaryotic cells, a specific set of proteins are modified by C-terminal attachment of 15-carbon farnesyl groups or 20-carbon geranylgeranyl groups that function both as anchors for fixing proteins to membranes and as molecular handles for facilitating binding of these lipidated proteins to other proteins. Additional modification of these prenylated proteins includes C-terminal proteolysis and methylation, and attachment of a 16-carbon palmitoyl group; these modifications augment membrane anchoring and alter the dynamics of movement of proteins between different cellular membrane compartments. The enzymes in the protein prenylation pathway have been isolated and characterized. Blocking protein prenylation is proving to be therapeutically useful for the treatment of certain cancers, infection by protozoan parasites and the rare genetic disease Hutchinson-Gilford progeria syndrome.

Original languageEnglish (US)
Pages (from-to)518-528
Number of pages11
JournalNature chemical biology
Volume2
Issue number10
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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