Journal of Biological Chemistry
Volume 272, Issue 46, 14 November 1997, Pages 28954-28961
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NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
KEX2 Influences Candida albicans Proteinase Secretion and Hyphal Formation*

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Candida albicans possesses at least seven differentially expressed genes that encode virulence-related secretory aspartyl proteinases (Saps). Sap DNA sequences predict post-translational processing at lysine-arginine residues in the preproteins, reminiscent of the maturation of Saccharomyces cerevisiae α-factor, where a prepropolypeptide is converted into a biologically active pheromone by Kex2, a subtilisin-like proprotein convertase. To investigate involvement of a C. albicans KEX2 homologue in Sap activation, a genetic selection was performed based on KEX2 function. A kex2strain of S. cerevisiae was transformed with a C. albicans genomic DNA library and screened for the production of active α-factor. Positive clones were assayed for killer toxin activity, another Kex2-dependent phenotype. Plasmids that rescued both defects contained a sequence encoding a protein homologous to S. cerevisiae Kex2. Both alleles of the C. albicans KEX2 were inactivated by successive mutations. Null mutants continued to secrete active Sap2; however, the enzyme was abnormally processed and secreted at reduced levels. Unexpectedly, null mutants were incapable of forming hyphae, instead differentiating into aberrantly shaped cells. The ability to normally process Sap2 and form hyphae was restored upon transformation of null mutants with aKEX2-containing plasmid.

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*

This work was supported by National Institutes of Health Grants PO1 DE07946 (to N. A. and the University of California at San Francisco Oral AIDS Center) and RO1 A133317 (to N. A.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.