Comparative analysis of programmed cell death pathways in filamentous fungi.
Comparative analysis of programmed cell death pathways in filamentous fungi.
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DOI：
10.1186/1471-2164-6-177
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发表时间：
2005-12-08
期刊：
影响因子：
4.4
通讯作者：
Nierman WC
中科院分区：
文献类型：
--
作者：
Fedorova ND;Badger JH;Robson GD;Wortman JR;Nierman WC
真菌在暴露于抗真菌剂、发育信号和应激因素时可经历自噬型或自噬型程序性细胞死亡（PCD）。丝状真菌也可以表现出一种称为异核体不相容性（HI）的细胞死亡形式，由两个遗传不相容的个体之间的融合引发。随着最近测序的烟曲霉和几个相关物种的基因组的可用性，我们能够定义真菌特异性死亡途径和所有真菌和后生动物共享的祖先核心凋亡机制的推定组件。系统发育分析HI相关蛋白从四个真菌和其他七种真菌揭示谱系特异性蛋白质家族，孤儿基因，和核心基因保守的所有真菌和后生动物。的拟南芥特异性结构域架构包括NACHT家族的NTPases，这可能是压力和养分供应信号的关键集成。通常发现它们与推定的效应子结构域如Pfs、SesB/利帕和新鉴定的结构域HET-s/LopB融合。许多推定的HI诱导剂和介质是丝状真菌特异性的，而在单细胞酵母中没有发现。除了它们在HI中的作用之外，它们中的一些似乎参与细胞周期、发育和性分化的调节。最后，酵母菌具有哺乳动物细胞凋亡机制的许多推定的下游组分，包括在模型酵母酿酒酵母中未发现的几种蛋白质。我们的分析确定了100多个假定的PCD相关基因在曲霉菌，这可能有助于扩大范围，目前可用的治疗曲霉病和其他侵袭性真菌疾病。该列表包括物种特异性蛋白质家族以及真菌和后生动物共享的祖先PCD机制的保守核心组件。
Fungi can undergo autophagic- or apoptotic-type programmed cell death (PCD) on exposure to antifungal agents, developmental signals, and stress factors. Filamentous fungi can also exhibit a form of cell death called heterokaryon incompatibility (HI) triggered by fusion between two genetically incompatible individuals. With the availability of recently sequenced genomes of Aspergillus fumigatus and several related species, we were able to define putative components of fungi-specific death pathways and the ancestral core apoptotic machinery shared by all fungi and metazoa. Phylogenetic profiling of HI-associated proteins from four Aspergilli and seven other fungal species revealed lineage-specific protein families, orphan genes, and core genes conserved across all fungi and metazoa. The Aspergilli-specific domain architectures include NACHT family NTPases, which may function as key integrators of stress and nutrient availability signals. They are often found fused to putative effector domains such as Pfs, SesB/LipA, and a newly identified domain, HET-s/LopB. Many putative HI inducers and mediators are specific to filamentous fungi and not found in unicellular yeasts. In addition to their role in HI, several of them appear to be involved in regulation of cell cycle, development and sexual differentiation. Finally, the Aspergilli possess many putative downstream components of the mammalian apoptotic machinery including several proteins not found in the model yeast, Saccharomyces cerevisiae. Our analysis identified more than 100 putative PCD associated genes in the Aspergilli, which may help expand the range of currently available treatments for aspergillosis and other invasive fungal diseases. The list includes species-specific protein families as well as conserved core components of the ancestral PCD machinery shared by fungi and metazoa.
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