Diverse Hap43-independent functions of the Candida albicans CCAAT-binding Complex
- Authors
- Hsu, P.C., Chao, C.C., Yang, C.Y., Ye, Y.L., Liu, F.C., Chuang, Y.J., and Lan, C.Y.
- ID
- ZDB-PUB-130412-11
- Date
- 2013
- Source
- Eukaryotic Cell 12(6): 804-15 (Journal)
- Registered Authors
- Chuang, Yung-Jen
- Keywords
- none
- MeSH Terms
-
- Animals
- CCAAT-Binding Factor/genetics*
- CCAAT-Binding Factor/metabolism
- Candida albicans/genetics*
- Candida albicans/metabolism
- Candida albicans/pathogenicity*
- Candidiasis/microbiology
- Candidiasis/mortality
- Cation Transport Proteins/genetics
- Cation Transport Proteins/metabolism
- Fungal Proteins/genetics*
- Fungal Proteins/metabolism
- GTP Phosphohydrolases/genetics
- GTP Phosphohydrolases/metabolism
- Gene Expression Regulation, Fungal*
- Iron/metabolism
- Mice
- Mitogen-Activated Protein Kinases/genetics
- Mitogen-Activated Protein Kinases/metabolism
- Mutation
- Promoter Regions, Genetic
- Repressor Proteins/genetics
- Repressor Proteins/metabolism
- Signal Transduction
- Survival Analysis
- TOR Serine-Threonine Kinases/genetics
- TOR Serine-Threonine Kinases/metabolism
- Virulence
- Zebrafish
- ras Proteins/genetics
- ras Proteins/metabolism
- PubMed
- 23543673 Full text @ Eukaryot. Cell
The CCAAT-motif is ubiquitous in promoters of eukaryotic genomes. The CCAAT-binding complex (CBC) is conserved across a wide range of organisms and specifically recognizes the CCAAT-motif and modulates transcription directly or in cooperation with other transcription factors. In Candida albicans, CBC is known to interact with the repressor Hap43 to negatively regulate iron-utilization genes in response to iron deprivation. However, the extent of additional functions of the CBC is unclear. In this study, we explored the new roles of CBC in C. albicans and found that CBC pleiotropically regulates many virulence traits in vitro, including negative control of genes responsible for ribosome biogenesis and translation, and positive regulation of low nitrogen—induced filamentation. In addition, C. albicans CBC involved in utilization of host proteins as nitrogen sources, and in repression of cellular flocculation and adhesin gene expression. Moreover, our epistasis analyses suggest that CBC acts as a downstream effector of Rhb1-TOR signaling and controls low nitrogen—induced filamentation via the Mep2-Ras1-PKA/MAPK pathway. Importantly, the phenotypes identified here are all independent of Hap43. Finally, deletion of genes encoding CBC components slightly attenuated C. albicans virulence in both zebrafish and murine models of infection. Our results thus highlight the new role of C. albicans CBC in regulating multiple virulence traits in response to environmental perturbations, and finally suggesting potential targets for antifungal therapies, and extend understanding of pathogenesis of other fungal pathogens.