Regulation of the Candida albicans hypha-inducing transcription factor Ume6 by the CDK1 cyclins Cln3 and Hgc1

Sigal Mendelsohn, Mariel Pinsky, Ziva Weissman, Daniel Kornitzer

Research output: Contribution to journalArticlepeer-review

Abstract

The ability to switch between proliferation as yeast cells and development into hyphae is a hallmark of Candida albicans. The switch to hyphal morphogenesis depends on external inducing conditions, but its efficiency is augmented in stationary-phase cells. Ume6, a transcription factor that is itself transcriptionally induced under hypha-promoting conditions, is both necessary and sufficient for hyphal morphogenesis. We found that Ume6 is regulated posttranslationally by the cell cycle kinase Cdc28/Cdk1, which reduces Ume6 activity via different mechanisms using different cyclins. Together with the cyclin Hgc1, Cdk1 promotes degradation of Ume6 via the SCFCDC4 ubiquitin ligase. Since HGC1 is a key transcriptional target of Ume6, this results in a negative-feedback loop between Hgc1 and Ume6. In addition, we found that Cln3, a G1 cyclin that is essential for cell cycle progression and yeast proliferation, suppresses hyphal morphogenesis and that Cln3 suppresses Ume6 activity both in the heterologous Saccharomyces cerevisiae system and in C. albicans itself. This activity of Cln3 may provide the basis for the antagonistic relationship between yeast proliferation and hyphal development in C. albicans.

Original languageEnglish
Article numbere00248-16
JournalmSphere
Volume2
Issue number2
DOIs
StatePublished - 1 Mar 2017

Keywords

  • Candida albicans
  • Cdc4
  • Cln3
  • Hgc1
  • Morphogenesis
  • SCF

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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