共查询到20条相似文献,搜索用时 31 毫秒
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Mathew A Mathur SK Jolly C Fox SG Kim S Morimoto RI 《Molecular and cellular biology》2001,21(21):7163-7171
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The expression patterns of two mammalian heat shock factors (HSFs) were analysed in cell systems known to reflect an altered heat shock response. For being able to discriminate between the two closely related factors HSF 1 and HSF 2, specific cDNA sequences were cloned and used to generate antisense RNAs as hybridization probes. In general, in various cell lines expression of the two heat shock factors was clearly different. These expression patterns of the HSF genes were not influenced by retinoic acid-induced differentiation of human NT2 and mouse F9 teratocarcinoma cells. Generally, HSF 2 expression was extremely low, whereas the significantly higher expression of HSF 1 revealed cell specific differences. The highest expression rates of both HSFs were observed in 293 cells. To examine whether these high levels are involved in the constitutive expression of heat shock genes in these cells, we analysed the binding pattern of 293 cell proteins to the heat shock elements (HSEs). As with other cells, HSE-binding activity in 293 cells was only observed after heat shock treatment. This points to an HSE-independent way for high level expression of heat shock genes in these cells. 相似文献
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Tanikawa J Ichikawa-Iwata E Kanei-Ishii C Nakai A Matsuzawa S Reed JC Ishii S 《The Journal of biological chemistry》2000,275(20):15578-15585
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Shinkawa T Tan K Fujimoto M Hayashida N Yamamoto K Takaki E Takii R Prakasam R Inouye S Mezger V Nakai A 《Molecular biology of the cell》2011,22(19):3571-3583
Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through αB-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases. 相似文献
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Inhibitors of the heat shock response: biology and pharmacology 总被引:2,自引:0,他引:2
A number of human diseases can be linked to aberrations in protein folding which cause an imbalance in protein homeostasis. Molecular chaperones, including heat shock proteins, act to assist protein folding, stability and activity in the cell. Attention has begun to focus on modulating the expression and/or activity of this group of proteins for the treatment of a wide variety of human diseases. This review will describe the progress made to date in developing pharmacological modulators of the heat shock response, including both agents which affect the entire heat shock response and those that specifically target the HSP70 and HSP90 chaperone families. 相似文献
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Activation of heat shock genes is not necessary for protection by heat shock transcription factor 1 against cell death due to a single exposure to high temperatures 下载免费PDF全文
Inouye S Katsuki K Izu H Fujimoto M Sugahara K Yamada S Shinkai Y Oka Y Katoh Y Nakai A 《Molecular and cellular biology》2003,23(16):5882-5895