Chaperoning parasitism: the importance of molecular chaperones in pathogen virulence.
Chaperoning parasitism: the importance of molecular chaperones in pathogen virulence.
复制标题
陪伴寄生：分子伴侣在病原体毒力中的重要性。
DOI：
10.1017/s0031182014000778
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发表时间：
2014
期刊：
影响因子：
2.4
通讯作者：
Neckers,Len
中科院分区：
文献类型：
--
作者：
Tatu,Utpal;Neckers,Len
传染性生物体在感染过程中必须应对苛刻且快速变化的环境。这对于利用不同宿主（例如昆虫和人类）来完成其生命周期的病原体尤其相关。其他可能影响病原体生存的环境挑战通常是在宿主对感染的反应中引发的。因此，毫不奇怪，许多成功的病原体不仅选择了宿主伴侣机制，而且还开发了自己强大的伴侣系统来克服与多个宿主感染和繁殖相关的压力。在过去的二十年中，人们对分子伴侣热休克蛋白 90 (Hsp90) 的性质和功能有了很多了解，特别是它与维持正常细胞稳态同时促进癌症发生、生长和存活的几个重要分子和途径的关联。 Hsp90 是一种丰富的（总细胞蛋白的 2-5%）分子伴侣，其稳态功能包括稳定和调节构成各种细胞信号节点的许多蛋白质（客户），以及促进细胞对环境压力的反应（Picard, 2002; Wandinger et al. 2008; Taipale et al. 2010）。伴侣分子被癌细胞“劫持”，这可以被视为“成瘾”，导致其表达升高至高于未转化细胞的表达水平（Trepel et al. 2010）。与癌症一样，许多病原体利用宿主细胞蛋白质稳定机制的各种成分来支持其感染性和复制。最近，分子伴侣，包括但不限于Hsp90，已被确定为病原体感染的毒力因子。就原生动物寄生虫而言，Hsp90 与昆虫向宿主形式的转化、增殖和耐药性有关（Neckers 和 Tatu，2008）。重要的是，宿主和寄生虫都表达
Infectious organisms have to cope with demanding and rapidly changing environments during infection. This is particularly relevant for pathogens that utilize different hosts (eg insects and humans) to complete their life cycle. Other environmental challenges that may affect pathogen survival are often triggered in the host in response to infection. It is not surprising, therefore, that many successful pathogens not only co-opt the host chaperone machinery but also have developed their own robust chaperone systems to overcome the stresses associated with infection and propagation in multiple hosts. During the past two decades much has been learned about the nature and function of the molecular chaperone heat shock protein 90 (Hsp90), especially concerning its association with several molecules and pathways important in maintaining normal cellular homoeostasis while also promoting cancer initiation, growth and survival. Hsp90 is an abundant (2–5% of total cellular protein) molecular chaperone whose homoeostatic functions include stabilization and modulation of a number of proteins (clients) that comprise various cell signalling nodes, and fostering cellular responses to environmental stress (Picard, 2002; Wandinger et al. 2008; Taipale et al. 2010). The chaperone is ‘hijacked’, in what could be regarded as an ‘addiction’, by cancer cells, causing its expression to be elevated above that of non-transformed cells (Trepel et al. 2010). Like cancer, numerous pathogens have co-opted various components of the host cellular proteostasis machinery to support their infectivity and replication. Recently, molecular chaperones, including but not limited to Hsp90, have been identified as virulence factors in pathogenic infections. In the case of protozoan parasites, Hsp90 has been implicated in conversion from insect to host forms, in proliferation, and in drug resistance (Neckers and Tatu, 2008). Importantly, both the host and the parasite express