Role of the 14-3-3 protein in carbon metabolism of the pathogenic yeast Candida albicans.

We previously demonstrated that the pathogenic yeast Candida albicans effectively adapts to utilize L-sorbose (Sou+) by a novel mechanism based on the loss of one copy of chromosome 5, probably due to the reduction of copy number of a negative regulator located on this chromosome. We report here another negative regulator of L-sorbose utilization, an orthologue of the Saccharomyces cerevisiae BMH1 gene, which encodes the evolutionarily conserved protein 14-3-3. This essential gene is located on chromosome 1, does not have paralogues, and is supposedly a component of the regulatory network. Experiments involving disruption of one allele of BMH1 and overexpression of BMH1 revealed that BMH1 represses the transcription of SOU1, which is responsible for the utilization of L-sorbose. Although the exact mechanism of the interaction between BMH1 and SOU1 is not known, it is clear that the control is based on the ratio of gene copy number, and that BMH1 does not control the loss of chromosome 5, the major mechanism producing Sou+ mutants. We propose that function of BMH1 as a negative regulator of SOU1 contributes to a general cellular homeostasis. This is a first report on the role of the C. albicans essential gene BMH1 as a negative regulator of the utilization of secondary carbon source in yeast, which further substantiates the involvement of 14-3-3 proteins in diverse functions. Copyright 2004 John Wiley & Sons, Ltd.