G1/S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans
G1/S Transcription Factor Orthologues Swi4p and Swi6p Are Important but Not Essential for Cell Proliferation and Influence Hyphal Development in the Fungal Pathogen Candida albicans
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DOI：
10.1128/ec.00278-10
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发表时间：
2011-03-01
期刊：
影响因子：
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通讯作者：
Bachewich, Catherine
中科院分区：
文献类型：
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作者：
Hussein, Bahira;Huang, Hao;Bachewich, Catherine
G（1）/S转换是细胞增殖的关键控制点，并且涉及在酿酒酵母中称为SBF和MBF或在粟酒裂殖酵母中称为MBF的必需转录复合物。在真菌病原体白色念珠菌中，G（1）/S调控尚不清楚。为了更深入地了解G（1）/S电路，我们表征了Swi 6p，Swi 4p和Mbp 1 p，它们是S中SBF（Swi 6p和Swi 4p）和MBF（Swi 6p和Mbp 1 p）组分的最接近的直系同源物。啤酒。mbp 1 Delta/Delta细胞表现出轻微的生长缺陷，而swi 4 Delta/Delta和swi 6 Delta/Delta酵母细胞的大小显著增加，表明G（1）期延迟。转录谱的基因集富集分析（GSEA）显示与G（1）/S期相关的基因在缺乏Swi 4p和Swi 6p的细胞中显著富集。这些表达模式表明Swi 4p和Swi 6p具有抑制和激活活性。有趣的是，swi 4 Delta/Delta swi 6 Delta/Delta和swi 4 Delta/Delta mbp 1 Delta/Delta菌株是存活的，与S.酿酒酵母，并表现出多效性表型，包括多芽酵母，假菌丝，有趣的是，真正的菌丝。一致地，GSEA鉴定了在C.白念珠菌-宿主细胞相互作用。由于Swi 4p和Swi 6p影响G（1）期进程，并且C.白念珠菌基因组中，这些因素可能有助于MBF活性。总体而言，数据表明，假定的G（1）/S调节机制的C。白色念珠菌包含新的特征，并强调了病原体中G（1）期和形态发生转换（包括菌丝发育）之间的关系。
The G(1)/S transition is a critical control point for cell proliferation and involves essential transcription complexes termed SBF and MBF in Saccharomyces cerevisiae or MBF in Schizosaccharomyces pombe. In the fungal pathogen Candida albicans, G(1)/S regulation is not clear. To gain more insight into the G(1)/S circuitry, we characterized Swi6p, Swi4p and Mbp1p, the closest orthologues of SBF (Swi6p and Swi4p) and MBF (Swi6p and Mbp1p) components in S. cerevisiae. The mbp1 Delta/Delta cells showed minor growth defects, whereas swi4 Delta/Delta and swi6 Delta/Delta yeast cells dramatically increased in size, suggesting a G(1) phase delay. Gene set enrichment analysis (GSEA) of transcription profiles revealed that genes associated with G(1)/S phase were significantly enriched in cells lacking Swi4p and Swi6p. These expression patterns suggested that Swi4p and Swi6p have repressing as well as activating activity. Intriguingly, swi4 Delta/Delta swi6 Delta/Delta and swi4 Delta/Delta mbp1 Delta/Delta strains were viable, in contrast to the situation in S. cerevisiae, and showed pleiotropic phenotypes that included multibudded yeast, pseudohyphae, and intriguingly, true hyphae. Consistently, GSEA identified strong enrichment of genes that are normally modulated during C. albicans-host cell interactions. Since Swi4p and Swi6p influence G(1) phase progression and SBF binding sites are lacking in the C. albicans genome, these factors may contribute to MBF activity. Overall, the data suggest that the putative G(1)/S regulatory machinery of C. albicans contains novel features and underscore the existence of a relationship between G(1) phase and morphogenetic switching, including hyphal development, in the pathogen.