Vos Michel J, Hageman Jurre, Carra Serena, Kampinga Harm H
Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Biochemistry. 2008 Jul 8;47(27):7001-11. doi: 10.1021/bi800639z. Epub 2008 Jun 17.
Heat shock proteins (HSPs) were originally identified as stress-responsive proteins required to deal with proteotoxic stresses. Besides being stress-protective and possible targets for delaying progression of protein folding diseases, mutations in chaperones also have been shown to cause disease (chaperonopathies). The mechanism of action of the "classical", stress-inducible HSPs in serving as molecular chaperones preventing the irreversible aggregation of stress-unfolded or disease-related misfolded proteins is beginning to emerge. However, the human genome encodes several members for each of the various HSP families that are not stress-related but contain conserved domains. Here, we have reviewed the existing literature on the various members of the human HSPB (HSP27), HSPH (HSP110), HSPA (HSP70), and DNAJ (HSP40) families. Apart from structural and functional homologies, several diversities between members and families can be found that not only point to differences in client specificity but also seem to serve differential client handling and processing. How substrate specificity and client processing is determined is far from being understood.
热休克蛋白（HSPs）最初被鉴定为应对蛋白毒性应激所需的应激反应蛋白。除了具有应激保护作用以及可能成为延缓蛋白质折叠疾病进展的靶点外，伴侣蛋白中的突变也已被证明会引发疾病（伴侣蛋白病）。“经典的”、应激诱导的热休克蛋白作为分子伴侣，防止应激解折叠或疾病相关错误折叠蛋白发生不可逆聚集的作用机制正逐渐显现。然而，人类基因组为各个不同的热休克蛋白家族编码了多个成员，这些成员与应激无关，但含有保守结构域。在此，我们综述了关于人类HSPB（HSP27）、HSPH（HSP110）、HSPA（HSP70）和DNAJ（HSP40）家族各成员的现有文献。除了结构和功能上的同源性外，还能发现成员之间以及家族之间的一些差异，这些差异不仅表明了底物特异性的不同，似乎还用于不同底物的处理和加工。底物特异性和底物处理是如何确定的，目前还远未明确。
