PXF, A PRENYLATED PROTEIN OF PEROXISOMES

CAAX farnesyltransferase attaches a farnesyl group to proteins that te rminate in the sequence CAAX, where C is cysteine, A is an aliphatic a mino acid, and X is typically methionine or serine. A limited number o f substrates for the CAAX farnesyltransferase have been identified in cultured cells. These include p21(ras) proteins and the nuclear lamins A and B. We describe here the use of a CAAX farnesyltransferase inhib itor, together with a hamster cell line that exhibits efficient uptake of [H-3]mevalonate, as a means of identifying novel farnesylated prot eins. One candidate protein was purified and its attached prenyl group identified as farnesyl. The predicted amino acid sequence of this pro tein, deduced from a cloned cDNA, terminates with the tetrapeptide Cys -Leu-Ile-Met, which conforms to the consensus sequence for recognition by farnesyltransferase. This farnesylated protein, designated PxF, is localized to the outer surface of peroxisomes as determined by indire ct immunofluorescence and electron microscopy.