...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>mSphere >Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans
【24h】

Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans

机译：碱性蛋白核集片中的非典型AP-1样转录因子YAP1的调节机制

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

AP-1-like transcription factors play evolutionarily conserved roles as redox sensors in eukaryotic oxidative stress responses. In this study, we aimed to elucidate the regulatory mechanism of an atypical yeast AP-1-like protein, Yap1, in the stress response and virulence of Cryptococcus neoformans . YAP1 expression was induced and involved not only by oxidative stresses, such as Hsub2/subOsub2/sub and diamide, but also by other environmental stresses, such as osmotic and membrane-destabilizing stresses. Yap1 was distributed throughout both the cytoplasm and the nucleus under basal conditions and more enriched within the nucleus in response to diamide but not to other stresses. Deletion of the C-terminal cysteine-rich domain (c-CRD), where the nuclear export signal resides, increased nuclear enrichment of Yap1 under basal conditions and altered resistance to oxidative stresses but did not affect the role of Yap1 in other stress responses and cellular functions. As a potential upstream regulator of Yap1, we discovered that Mpk1 is positively involved, but Hog1 is mostly dispensable. Pleiotropic roles for Yap1 in diverse biological processes were supported by transcriptome data showing that 162 genes are differentially regulated by Yap1, with further analysis revealing that Yap1 promotes cellular resistance to toxic cellular metabolites produced during glycolysis, such as methylglyoxal. Finally, we demonstrated that Yap1 plays a minor role in the survival of C. neoformans within hosts. IMPORTANCE The human meningitis fungal pathogen, Cryptococcus neoformans , contains the atypical yeast AP-1-like protein Yap1. Yap1 lacks an N-terminal cysteine-rich domain (n-CRD), which is present in other fungal Yap1 orthologs, but has a C-terminal cysteine-rich domain (c-CRD). However, the role of c-CRD and its regulatory mechanism remain unknown. Here, we report that Yap1 is transcriptionally regulated in response to oxidative, osmotic, and membrane-destabilizing stresses partly in an Mpk1-dependent manner, supporting its role in stress resistance. The c-CRD domain contributed to the role of Yap1 only in resistance to certain oxidative stresses and azole drugs but not in other cellular functions. Yap1 has a minor role in the survival of C. neoformans in a murine model of systemic cryptococcosis.
机译：AP-1样转录因子在真核氧化应激应答中的氧化还原传感器发挥作用。在这项研究中，我们旨在阐明含有非典型酵母AP-1样蛋白YAP1的调节机制，在密码反应和粘性球菌癌的应力反应和毒力。 yap1表达不仅致氧化应力，例如H 2 o 2 和酰胺，还涉及其他环境应力，例如渗透渗透和膜 - 稳定的应力。在基础条件下，yap1分布在整个细胞质和细胞核下，响应于酰胺而不是其他应力，在细胞质下分布。缺失C末端半胱氨酸富域（C-CRD），在核导出信号所在，在基础条件下增加YAP1的核富集，并改变对氧化胁迫的抗性，但不影响YAP1在其他应激反应中的作用和蜂窝功能。作为YAP1的潜在上游调节器，我们发现MPK1积极涉及，但HOG1大多是可分配的。在不同的生物过程中的百分比作用是通过转录组数据支持的，表明162个基因由YAP1差异化，进一步分析显示YAP1促进糖醇类期间产生的细胞抗性对糖醇类产生的有毒细胞代谢物。最后，我们证明YAP1在宿主内C.新纪元的存活中发挥着小小的作用。重要性人脑膜炎真菌病原体，含有非典型酵母AP-1样蛋白YAP1。 YAP1缺乏N-末端半胱氨酸的结构域（N-CRD），其存在于其他真菌YAP1矫形器中，但具有C-末端半胱氨酸的结构域（C-CRD）。但是，C-CRD的作用及其监管机制仍然未知。在此，我们报告说，YAP1响应于氧化，渗透性和膜 - 稳定应力部分以MPK1依赖性方式进行转录调节，支持其在应力抗性中的作用。 C-CRD结构域有助于YAP1仅在抗氧化氧化应力和唑类药物的作用，而不是在其他细胞功能中的作用。 YAP1在全身性密集菌病的小鼠模型中的C. Neoformans的存活中具有次要作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号