Protein prenyltransferases: anchor size, pseudogenes and parasites.
Lipid modification of eukaryotic proteins by protein prenyltransferases is required for critical signaling pathways, cell cycle progression, cytoskeleton remodeling, induction of apoptosis and vesicular trafficking. This review analyzes the influence of distinct states of sequential posttranslational processing that can be obtained after single or double prenylation, reversible palmitoylation, proteolytic cleavage of the C-terminus and possible reversible carboxymethylation. This series of modifications, as well as the exact length of the prenyl anchor, are determinants in protein-membrane and specific protein-protein interactions of protein prenyltransferase substrates. Furthermore, the occurrence and distribution of pseudogenes of protein prenyltransferase subunits are discussed. Besides being developed as anti-cancer agents, prenyltransferase inhibitors are effective against an increasing number of parasitic diseases. Extensive screens for protein prenyltransferases in genomic data of fungal and protozoan pathogens unveil a series of new pharmacologic targets for prenyltransferase inhibition, including the parasites Brugia malayi, Onchocerca volvulus, Aspergillus nidulans, Pneumocystis carinii, Entamoeba histolytica, Strongyloides stercoralis, Trichinella spiralis and Cryptosporidium parvum.
Maurer-Stroh
Sebastian
S
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. stroh@imp.univie.ac.at
Washietl
Stefan
S
Eisenhaber
Frank
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004122:Dimethylallyltranstransferase / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010271:Parasites / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D010944:Plants / Q000469:parasitology; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D011544:Pseudogenes / Q000502:physiology*; D013379:Substrate Specificity; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004122:Dimethylallyltranstransferase; D020691:rab GTP-Binding Proteins; D018631:ras Proteins