1887

Abstract

While searching for regulators of virulence attributes of the human-pathogenic fungus , a gene was identified similar to the genes encoding the mammalian phospholipase A2-activating protein (PLAP) and the 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. was expressed under all conditions investigated. Gene disruption of 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 were filamentous and grew as pseudohyphae and true hyphae under conditions that normally support yeast growth. Transcriptional profiling of Δ indicated that several genes associated with Ub-mediated proteolysis, including and , are upregulated. These data suggest that of , like its orthologue in , is associated with Ub-mediated proteolysis and has multiple functions. However, some functions of CaDoa1 seem to be unique for . These results support the hypothesis that Ub-mediated proteolysis plays an important role in the regulation of morphology in .

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2007-04-01
2020-08-03
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