title: SUMOylation of Wor1 by a novel SUMO E3 ligase controls cell fate in Candida albicans.
abstract: Candida albicans is the most common human fungal pathogen, yet is a normal commensal resident of the human gut. CO(2) levels in the gut are much higher than in air, and it is known that elevated CO(2) concentration promotes C. albicans cells to undergo a phenotypic switch from white to opaque phase. Wor1, the master regulator of opaque cell formation, is required for both the white to opaque transition and opaque maintenance. To elucidate the regulatory mechanism of Wor1, we set out to identify Wor1-interacting proteins using a yeast two-hybrid screen. A SUMO E3 ligase named Wos1 (Wor1 SUMO-ligase 1) was identified to interact with Wor1 and regulate Wor1 SUMOylation. WOS1 expression is upregulated in response to high CO(2), and the induction by CO(2) is dependent on the transcription factor Flo8. Under high CO(2) conditions, Wos1 is required for the white to opaque switch and acts downstream of Flo8. At atmospheric CO(2) levels, overexpression of Wos1 enhances Wor1 SUMOylation and promotes the white to opaque switch. Wor1 is found to be SUMOylated at lysine 385, and loss of this mark by point mutation leads to a defect in CO(2) -mediated opaque cell induction. Together, our genetic and biological data show that Wos1-mediated Wor1 SUMOylation contributes to the regulation of CO(2) -induced white to opaque switching as well as heritable maintenance of the opaque cell type.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Biological Chemistry, University of California, Irvine, USA.
authors.forename: Haoping
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Jiangye
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D058207:Sumoylation; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D002245:Carbon Dioxide; D044767:Ubiquitin-Protein Ligases