Pex19p, a Farnesylated Protein Essential for Peroxisome Biogenesis

ABSTRACT

We report the identification and molecular characterization of Pex19p, an oleic acid-inducible, farnesylated protein of 39.7 kDa that is essential for peroxisome biogenesis in Saccharomyces cerevisiae. Cells lacking Pex19p are characterized by the absence of morphologically detectable peroxisomes and mislocalization of peroxisomal matrix proteins to the cytosol. The human HK33 gene product was identified as the putative human ortholog of Pex19p. Evidence is provided that farnesylation of Pex19p takes place at the cysteine of the C-terminal CKQQ amino acid sequence. Farnesylation of Pex19p was shown to be essential for the proper function of the protein in peroxisome biogenesis. Pex19p was shown to interact with Pex3p in vivo, and this interaction required farnesylation of Pex19p.

ACKNOWLEDGMENTS

K.G., W.G., and M.L. contributed equally to this work.

We are grateful to all members of our labs for fruitful discussions. We thank Adalbert Roscher for kindly providing the HK33 gene. We thank Gabriele Dodt, Peter Rehling, and Michael Schwierskott for reading the manuscript.

This work was funded by grants from the Deutsche Forschungsgemeinschaft (Er178/2-1, Ku329/17-1, Ku329/17-2, and Ro 727/1-2) and by the Fonds der Chemischen Industrie.