Therapeutic intervention based on protein prenylation and associated modifications.
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.
Gelb
Michael H
MH
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. gelb@chem.washington.edu
Brunsveld
Lucas
L
Hrycyna
Christine A
CA
Michaelis
Susan
S
Tamanoi
Fuyuhiko
F
Van Voorhis
Wesley C
WC
Waldmann
Herbert
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011371:Progeria / Q000188:drug therapy* / Q000235:genetics; D017368:Protein Prenylation / Q000187:drug effects; D011506:Proteins / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D011506:Proteins