Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 19, Issue 5, Pages 2251-2266Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E07-09-0960
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Funding
- Swiss National Science Foundation [81BS-69445]
- Novartis Stiftung
- Freiwillige Akademische Gesellschaft
- European Commission [QLK2-2000-00795, MRTN-CT-2003-504148]
- EGIDE
- Institut Pasteur Programme Transversal de Recherche [173]
- National Institutes of Health [5R0 1DE017088]
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Members of the dual-specificity tyrosine-phosphorylated and regulated kinase (DYRK) family perform a variety of functions in eukaryotes. We used gene disruption, targeted pharmacologic inhibition, and genome-wide transcriptional profiling to dissect the function of the Yak1 DYRK in the human fungal pathogen Candida albicans. C. albicans strains with mutant yak1 alleles showed defects in the yeast-to-hypha transition and in maintaining hyphal growth. They also could not form biofilms. Despite their in vitro filamentation defect, C. albicans yak1 Delta/yak1 Delta mutants remained virulent in animal models of systemic and oropharyngeal candidiasis. Transcriptional profiling showed that Yak1 was necessary for the up-regulation of only a subset of hypha-induced genes. Although downstream targets of the Tec1 and Bcr1 transcription factors were down-regulated in the yak1 Delta/yak1 Delta mutant, TEC1 and BCR1 were not. Furthermore, 63% of Yak1-dependent, hypha-specific genes have been reported to be negatively regulated by the transcriptional repressor Tup1 and inactivation of TUP1 in the yak1 Delta/yak1 Delta mutant restored filamentation, suggesting that Yak1 may function upstream of Tup1 in governing hyphal emergence and maintenance.
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