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COP9 信号体介导真菌发育过程中激素、氧化应激保护和细胞壁重排的转录和代谢反应。

The COP9 signalosome mediates transcriptional and metabolic response to hormones, oxidative stress protection and cell wall rearrangement during fungal development.

机构信息

Institut für Mikrobiologie & Genetik, Georg-August-Universität, D-37077 Göttingen, Germany.

出版信息

Mol Microbiol. 2010 Nov;78(4):964-79. doi: 10.1111/j.1365-2958.2010.07384.x. Epub 2010 Sep 27.

Abstract

The COP9 signalosome complex (CSN) is a crucial regulator of ubiquitin ligases. Defects in CSN result in embryonic impairment and death in higher eukaryotes, whereas the filamentous fungus Aspergillus nidulans survives without CSN, but is unable to complete sexual development. We investigated overall impact of CSN activity on A. nidulans cells by combined transcriptome, proteome and metabolome analysis. Absence of csn5/csnE affects transcription of at least 15% of genes during development, including numerous oxidoreductases. csnE deletion leads to changes in the fungal proteome indicating impaired redox regulation and hypersensitivity to oxidative stress. CSN promotes the formation of asexual spores by regulating developmental hormones produced by PpoA and PpoC dioxygenases. We identify more than 100 metabolites, including orsellinic acid derivatives, accumulating preferentially in the csnE mutant. We also show that CSN is required to activate glucanases and other cell wall recycling enzymes during development. These findings suggest a dual role for CSN during development: it is required early for protection against oxidative stress and hormone regulation and is later essential for control of the secondary metabolism and cell wall rearrangement.

摘要

COP9 信号小体复合物(CSN)是泛素连接酶的关键调节剂。在高等真核生物中,CSN 的缺陷会导致胚胎损伤和死亡,而丝状真菌构巢曲霉在没有 CSN 的情况下仍能存活,但无法完成有性发育。我们通过对全转录组、蛋白质组和代谢组学分析,研究了 CSN 活性对构巢曲霉细胞的整体影响。csn5/csnE 的缺失会影响发育过程中至少 15%的基因的转录,包括许多氧化还原酶。csnE 缺失导致真菌蛋白质组发生变化,表明氧化还原调节受损和对氧化应激的敏感性增加。CSN 通过调节 PpoA 和 PpoC 双加氧酶产生的发育激素来促进无性孢子的形成。我们鉴定了 100 多种代谢物,包括欧栓酸衍生物,这些代谢物在 csnE 突变体中优先积累。我们还表明 CSN 在发育过程中需要激活葡聚糖酶和其他细胞壁回收酶。这些发现表明 CSN 在发育过程中具有双重作用:它早期需要保护免受氧化应激和激素调节,后期则需要控制次级代谢和细胞壁重排。

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