Isolation of ptb1, a gene for the beta-subunit of a prenyltransferase from fission yeast.

Modification of proteins at C-terminal cysteine residues by the isoprenoids farnesyl (C15) or geranylgeranyl (C20) is essential for the membrane association and biological function of several eukaryotic proteins (for reviews, see 1, 2). Farnesylation is signalled by a C-terminal -CAAX motif where C is cysteine, A is aliphatic and X is usually serine or methionine. Farnesyltransferase (FTase) utilises farnesyl diphosphate to modify the cysteine residue and processing is completed by proteolytic removal of the -AAX residues and carboxyl methylation of the C-terminal a-carboxyl group. There are two pathways for geranylgeranylation involving two distinct geranylgeranyltransferases (GGTase). The type4 enzyme (GGTase-I or CAAX-GGTase) recognises the -CAAX motif when X is leucine and is responsible for the geranylgeranylation of most proteins. A second geranylgeranyltransferase (GGTase-I1 or Rab-GGTase) is responsible for the geranylgeranylation of Rab proteins Rab proteins lack CAAX motifs but terminate in either CC or CXC and both cysteines can become modified (3). All three prenyltransferases are ap heterodimers. FTase and GGTase-I share a common a subunit (4) which is homologous to the a subunit of GGTase-11, while the three p subunits also share significant homology (5). Our understanding of prenylation has benefited from studies in the budding yeast Saccharomyces cerevisiae where each enzyme subunit has been identified. Studies in the distantly related fission yeast Schizosaccharomyces pombe are less well advanced although there is evidence for all three types of prenylation. The cwg2 gene for GGTase-IP has been isolated (6) and the farnesylation of the M-factor mating pheromone (7) and the geranylgeranylation of the Rab-like YPT proteins (8) have been described. We now describe the sequence of the gene for the GGTase-IIP from S.pombe.