New tricks for an old dog: The evolving world of Hsp70
New tricks for an old dog: The evolving world of Hsp70
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DOI：
10.1196/annals.1391.018
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Morano, Kevin A.
中科院分区：
文献类型：
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作者：
Morano, Kevin A.
Hsp 70分子伴侣可以说是热休克蛋白家族中研究最多的成员，这一遗产可以追溯到噬菌体遗传学的早期。然而，关于这种重要的蛋白质折叠机器还有很多东西需要了解。它参与了许多人类病理学，从癌症到蛋白质聚集疾病，强调了对Hsp 70所起的无数细胞作用和未决问题的全面理解的必要性。本文将探讨几个令人兴奋的途径研究的功能和生物学的伴侣。对许多真核Hsp 70亚型的分析表明，一些Hsp 70成员具有不同的功能作用，从蛋白质“折叠酶”过渡到伴侣辅因子。从结构研究中获得的新见解揭示了域间通信的可能模型，从而调节底物结合和加工。Hsp 70活性的小分子调节的进展可能具有显著的临床影响。也有越来越多的认识，热休克蛋白70参与不同的功能网络与其他蛋白伴侣。因此，该领域正处于一个令人兴奋的时刻，过去的巨大成功提供了一个坚实的框架，将用于推动发现和应用-Hsp 70，从分子到人。
The Hsp70 chaperone is arguably the most studied member of the heat shock protein family, a legacy traced back to the early days of phage genetics. However, much still remains to be learned about this essential protein-folding machine. Its involvement in a number of human pathologies, ranging from cancer to protein aggregation diseases, underscores the need for a comprehensive understanding of the myriad cellular roles Hsp70 plays and the outstanding open questions. This article will explore several exciting avenues of research into the function and biology of the chaperone. Analysis of the many eukaryotic Hsp70 isoforms has demonstrated distinct functional roles for some Hsp70 members, to the point of transition from a protein "foldase" to a chaperone cofactor. New insights gained from structural studies have unveiled a likely model for interdomain communication and thus regulation of substrate binding and processing. Advances in small molecule modulation of Hsp70 activity are likely to have significant clinical impact. There is also a growing realization that Hsp70 participates in distinct functional networks in partnership with other protein chaperones. The field is thus at an exciting time when the substantial successes of the past have provided a solid framework that will be used to fuel both discovery and application-Hsp70, from molecule to man.