Role for the SCFCDC4 ubiquitin ligase in candida albicans morphogenesis
Role for the SCFCDC4 ubiquitin ligase in candida albicans morphogenesis
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DOI：
10.1091/mbc.e05-01-0079
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发表时间：
2005-06-01
影响因子：
3.3
通讯作者：
Kornitzer, D
中科院分区：
文献类型：
--
作者：
Atir-Lande, A;Gildor, T;Kornitzer, D
白色念珠菌是一种主要的真菌病原体，它在酵母菌形式和菌丝（霉菌）形式之间转换的能力被认为是生物体入侵宿主并引起疾病的重要能力。我们发现，CaCDC4 （SCFCDC4泛素连接酶的酿酒酵母F-box蛋白组分的同源物）缺失的白色念珠菌突变体是可存活的，并表现出组成丝状（主要是菌丝）生长。SCFCaCDC4（-/-）突变体的表型表明，泛素介导的蛋白质降解参与了白色念珠菌二态开关的调节，酵母到霉菌开关的一个或多个调节因子位于SCFCaCDC4的底物中。上位分析表明，Cacdc4（-/-）表型在很大程度上独立于诱导成丝的转录因子Efg1和Cph1。我们鉴定了白色念珠菌Far1和Sol1，它们是cerevisiae SCFCDC4底物Far1和Sic1的同源物，并表明Sol1是白色念珠菌Cdc4的底物。这两种蛋白对Cacdc4（-/-）突变体的菌丝表型都不是必需的。然而，SOLI的异位表达和缺失表明该基因在白色念珠菌的形态发生中起作用。
The ability of Candida albicans, a major fungal pathogen, to switch between a yeast form, and a hyphal (mold) form is recognized as being important for the ability of the organism to invade the host and cause disease. We found that a C. albicans mutant deleted for CaCDC4, a homologue of the Saccharomyces cerevisiae F-box protein component of the SCFCDC4 ubiquitin ligase, is viable and displays constitutive filamentous, mostly hyphal, growth. The phenotype of the Cacdc4(-/-) mutant suggests that ubiquitin-mediated protein degradation is involved in the regulation of the dimorphic switch of C. albicans and that one or more regulators of the yeast-to-mold switch are among the substrates of SCFCaCDC4. Epistasis analysis indicates that the Cacdc4(-/-) phenotype is largely independent of the filamentation-inducing transcription factors Efg1 and Cph1. We identify C. albicans Far1 and Sol1, homologues of the S. cerevisiae SCFCDC4 substrates Far1 and Sic1, and show that Sol1 is a substrate of C. albicans Cdc4. Neither protein is essential for the hyphal phenotype of the Cacdc4(-/-) mutant. However, ectopic expression and deletion of SOLI indicate a role for this gene in C. albicans morphogenesis.