Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1

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...

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Autores principales:	Sigal Mendelsohn, Mariel Pinsky, Ziva Weissman, Daniel Kornitzer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Candida albicans Cdc4 Cln3 Hgc1 SCF morphogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/260b50c173ef4fc382a573160d1c76f4
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spelling	oai:doaj.org-article:260b50c173ef4fc382a573160d1c76f42021-11-15T15:21:45ZRegulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc110.1128/mSphere.00248-162379-5042https://doaj.org/article/260b50c173ef4fc382a573160d1c76f42017-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00248-16https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE The yeast to hypha (mold) morphogenetic switch of Candida albicans plays a role in its virulence and constitutes a diagnostic trait for this organism, the most prevalent systemic fungal pathogen in industrialized countries. It has long been known that hyphae are most efficiently induced from stationary cultures. Here, a molecular basis for this observation is provided. The G1 cyclin Cln3, an essential promoter of yeast proliferation, was found to suppress hyphal induction. Suppression of hyphal induction is achieved by inhibition of the activity of the central activator of hyphal morphogenesis, the transcription factor Ume6. Thus, levels of Cln3 control the switch between proliferation of C. albicans as individual yeast cells and development into extended hyphae, a switch that may preface the proliferation/differentiation switch in multicellular organisms.Sigal MendelsohnMariel PinskyZiva WeissmanDaniel KornitzerAmerican Society for MicrobiologyarticleCandida albicansCdc4Cln3Hgc1SCFmorphogenesisMicrobiologyQR1-502ENmSphere, Vol 2, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Cdc4 Cln3 Hgc1 SCF morphogenesis Microbiology QR1-502
spellingShingle	Candida albicans Cdc4 Cln3 Hgc1 SCF morphogenesis Microbiology QR1-502 Sigal Mendelsohn Mariel Pinsky Ziva Weissman Daniel Kornitzer Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
description	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. IMPORTANCE The yeast to hypha (mold) morphogenetic switch of Candida albicans plays a role in its virulence and constitutes a diagnostic trait for this organism, the most prevalent systemic fungal pathogen in industrialized countries. It has long been known that hyphae are most efficiently induced from stationary cultures. Here, a molecular basis for this observation is provided. The G1 cyclin Cln3, an essential promoter of yeast proliferation, was found to suppress hyphal induction. Suppression of hyphal induction is achieved by inhibition of the activity of the central activator of hyphal morphogenesis, the transcription factor Ume6. Thus, levels of Cln3 control the switch between proliferation of C. albicans as individual yeast cells and development into extended hyphae, a switch that may preface the proliferation/differentiation switch in multicellular organisms.
format	article
author	Sigal Mendelsohn Mariel Pinsky Ziva Weissman Daniel Kornitzer
author_facet	Sigal Mendelsohn Mariel Pinsky Ziva Weissman Daniel Kornitzer
author_sort	Sigal Mendelsohn
title	Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
title_short	Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
title_full	Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
title_fullStr	Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
title_full_unstemmed	Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1
title_sort	regulation of the <named-content content-type="genus-species">candida albicans</named-content> hypha-inducing transcription factor ume6 by the cdk1 cyclins cln3 and hgc1
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/260b50c173ef4fc382a573160d1c76f4
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Regulation of the <named-content content-type="genus-species">Candida albicans</named-content> Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1

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