Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals.
Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals.
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DOI：
10.1111/j.1365-2958.2009.06883.x
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发表时间：
2009-11
影响因子：
3.6
通讯作者：
Brown AJ
中科院分区：
文献类型：
--
作者：
Nicholls S;Leach MD;Priest CL;Brown AJ
所有生物都进化出了保护它们免受环境压力的机制。人类的主要真菌病原体白色念珠菌已经进化出强大的应激反应，保护其免受人类免疫防御并促进其致病性。然而，C.白色念珠菌不太可能暴露于热休克，因为它必然与温血动物相关。因此，我们研究了热休克转录因子（Hsf 1）在这种病原体中的作用。我们证明了C.白念珠菌表达一种进化上保守的Hsf 1（orf19.4775），其在热休克反应中被磷酸化，通过热休克元件（HSE）诱导转录，有助于对热休克的整体转录反应，并且对于生存力是必需的。为什么Hsf 1在这种专性动物的saplete中是保守的？我们推断Hsf 1可能有助于医学相关的应激反应。然而，事实并非如此，因为Hsf 1特异性HSE-lacZ报告基因不会被氧化、渗透、弱酸或pH应激激活。相反，在没有热休克的情况下，Hsf 1是必需的伴侣蛋白（例如Hsp 104、Hsp 90、Hsp 70）表达所必需的。此外，Hsf 1还调控了C.白色念珠菌。因此，Hsf 1在这种病原体中的主要作用可能是响应于生长温度的分子伴侣水平的稳态调节，而不是对突然的热转换的急性反应的激活。
All organisms have evolved mechanisms that protect them against environmental stress. The major fungal pathogen of humans, Candida albicans, has evolved robust stress responses that protect it against human immune defences and promote its pathogenicity. However, C. albicans is unlikely to be exposed to heat shock as it is obligatorily associated with warm-blooded animals. Therefore, we examined the role of the heat shock transcription factor (Hsf1) in this pathogen. We show that C. albicans expresses an evolutionarily conserved Hsf1 (orf19.4775) that is phosphorylated in response to heat shock, induces transcription via the heat shock element (HSE), contributes to the global transcriptional response to heat shock, and is essential for viability. Why has Hsf1 been conserved in this obligate animal saprophyte? We reasoned that Hsf1 might contribute to medically relevant stress responses. However, this is not the case, as an Hsf1-specific HSE-lacZ reporter is not activated by oxidative, osmotic, weak acid or pH stress. Rather, Hsf1 is required for the expression of essential chaperones in the absence of heat shock (e.g. Hsp104, Hsp90, Hsp70). Furthermore, Hsf1 regulates the expression of HSE-containing genes in response to growth temperature in C. albicans. Therefore, the main role of Hsf1 in this pathogen might be the homeostatic modulation of chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions.
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影响因子：
3.1
作者：
Bromuro, C;La Valle, R;Cassone, A
通讯作者：
Cassone, A
影响因子：
11.4
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3.3
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KINGSTON, RE
DOI：
10.1073/pnas.92.7.2994
发表时间：
1995-03-28
影响因子：
11.1
作者：
GEHRING, WJ;WEHNER, R
通讯作者：
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