The NDR Kinase Cbk1 Downregulates the Transcriptional Repressor Nrg1 through the mRNA-Binding Protein Ssd1 in Candida albicans
The NDR Kinase Cbk1 Downregulates the Transcriptional Repressor Nrg1 through the mRNA-Binding Protein Ssd1 in Candida albicans
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DOI：
10.1128/ec.00016-15
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发表时间：
2015-07-01
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影响因子：
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通讯作者：
Kim, Jeong-Yoon
中科院分区：
文献类型：
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作者：
Lee, Hye-Jeong;Kim, Jong-Myeong;Kim, Jeong-Yoon
NDR（核Dbf 2相关）激酶是极化形态发生、胞质分裂、细胞增殖和凋亡的必要组分。NDR激酶Cbk 1是白念珠菌菌丝生长所必需的，然而，Cbk 1在菌丝形态发生中的分子功能在很大程度上是未知的。在这里，我们报告说，Cbk 1下调转录抑制因子Nrg 1通过mRNA结合蛋白Ssd 1，其中有9个Cbk 1磷酸化的共识基序。我们发现SSD 1的缺失部分抑制了C.白色念珠菌cbk 1 Delta/Delta突变体和Ssd 1与Cbk 1物理相互作用。Ssd 1定位于极化生长位点需要Cbk 1。磷酸模拟SSD 1等位基因（ssd 1 - 9 E）允许Cbk 1 Delta/Delta突变体形成短菌丝，而磷酸缺陷SSD 1等位基因（ssd 1 -9A）导致菌丝比野生型SSD 1等位基因短，表明Cbk 1对Ssd 1的磷酸化对菌丝形态发生很重要。此外，我们表明，转录抑制因子Nrg 1不会消失在菌丝起始的cbk 1三角洲/三角洲突变体，但完全不存在的cbk 1三角洲/三角洲ssd 1三角洲/三角洲双突变体。SSD 1的缺失也增加了人胚肾细胞系HEK 293 T中Als 3的表达和cbk 1 Delta/Delta突变体的内化。综上所述，我们的研究结果表明，Cbk 1在C.白念珠菌是通过Ssd 1下调Nrg 1。
NDR (nuclear Dbf2-related) kinases are essential components for polarized morphogenesis, cytokinesis, cell proliferation, and apoptosis. The NDR kinase Cbk1 is required for the hyphal growth of Candida albicans; however, the molecular functions of Cbk1 in hyphal morphogenesis are largely unknown. Here, we report that Cbk1 downregulates the transcriptional repressor Nrg1 through the mRNA-binding protein Ssd1, which has nine Cbk1 phosphorylation consensus motifs. We found that deletion of SSD1 partially suppressed the defective hyphal growth of the C. albicans cbk1 Delta/Delta mutant and that Ssd1 physically interacts with Cbk1. Cbk1 was required for Ssd1 localization to polarized growth sites. The phosphomimetic SSD1 allele (ssd1-9E) allowed the cbk1 Delta/Delta mutant to form short hyphae, and the phosphodeficient SSD1 allele (ssd1-9A) resulted in shorter hyphae than did the wild-type SSD1 allele, indicating that Ssd1 phosphorylation by Cbk1 is important for hyphal morphogenesis. Furthermore, we show that the transcriptional repressor Nrg1 does not disappear during hyphal initiation in the cbk1 Delta/Delta mutant but is completely absent in the cbk1 Delta/Delta ssd1 Delta/Delta double mutant. Deletion of SSD1 also increased Als3 expression and internalization of the cbk1 Delta/Delta mutant in the human embryonic kidney cell line HEK293T. Collectively, our results suggest that one of the functions of Cbk1 in the hyphal morphogenesis of C. albicans is to downregulate Nrg1 through Ssd1.