Multiple functions of DOA1 in Candida albicans.
While searching for regulators of virulence attributes of the human-pathogenic fungus Candida albicans, a gene was identified similar to the genes encoding the mammalian phospholipase A2-activating protein (PLAP) and the Saccharomyces cerevisiae protein Doa1, which is known to play a key role during ubiquitin (Ub)-dependent protein degradation. All three proteins contain WD-repeats. Both PLAP and CaDoa1 contain a mellitin-like sequence with a central 'KVL'. This mellitin-like sequence was shown to be necessary for full function of CaDoa1. CaDOA1 was expressed under all conditions investigated. Gene disruption of CaDOA1 caused phenotypes including modified colony morphologies, temperature sensitivity, reduced secretion of hydrolytic enzymes and hypersensitivity to various compounds such as propranolol, butanol, caffeine, chelators, azoles, nocodazole and cadmium. Strikingly, mutants lacking DOA1 were filamentous and grew as pseudohyphae and true hyphae under conditions that normally support yeast growth. Transcriptional profiling of Deltadoa1 indicated that several genes associated with Ub-mediated proteolysis, including CDC48 and UBI4, are upregulated. These data suggest that DOA1 of C. albicans, like its orthologue in S. cerevisiae, is associated with Ub-mediated proteolysis and has multiple functions. However, some functions of CaDoa1 seem to be unique for C. albicans. These results support the hypothesis that Ub-mediated proteolysis plays an important role in the regulation of morphology in C. albicans.
Kunze
Donika
D
Robert Koch-Institut, Nordufer 20, D-13353, Berlin, Germany.
MacCallum
Donna
D
Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Odds
Frank C
FC
Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Hube
Bernhard
B
Department of Microbial Pathogenicity Mechanisms, Lelbniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena (HKI), Beutenbergstraße 11a, D-07745 Jena, Germany.|Friedrich-Schiller-University, Jena, Germany.|Robert Koch-Institut, Nordufer 20, D-13353, Berlin, Germany.
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D025301:Hyphae / Q000166:cytology; D008555:Melitten / Q000737:chemistry; D019216:Metals, Heavy / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010740:Phospholipases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; D005656:Fungal Proteins; D019216:Metals, Heavy; D008555:Melitten; D010740:Phospholipases