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J Biol Chem

Title:		KEX2 influences Candida albicans proteinase secretion and hyphal formation
Author(s):		Newport G; Agabian N;
Address:		"Department of Stomatology, University of California at San Francisco, San Francisco, California 94143-0422, USA"
Journal Title:		J Biol Chem
Year:		1997
Volume:		272
Issue:		46
Page Number:		28954 - 28961
DOI:		10.1074/jbc.272.46.28954
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"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 alpha-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 kex2 strain of S. cerevisiae was transformed with a C. albicans genomic DNA library and screened for the production of active alpha-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 a KEX2-containing plasmid"
Keywords:		"Amino Acid Sequence Aspartic Acid Endopeptidases/*metabolism Base Sequence Candida albicans/*enzymology/genetics/growth & development Cloning, Molecular DNA, Fungal Genetic Complementation Test Killer Factors, Yeast Mating Factor Molecular Sequence Data M;"
Notes:		"MedlineNewport, G Agabian, N eng P01 DE07946/DE/NIDCR NIH HHS/ R01 AI33317/AI/NIAID NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1997/11/20 J Biol Chem. 1997 Nov 14; 272(46):28954-61. doi: 10.1074/jbc.272.46.28954"