Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Int J Biochem Cell Biol. 2012 Oct;44(10):1706-10. doi: 10.1016/j.biocel.2012.06.005. Epub 2012 Jun 19.
Although initially somewhat ignored, recent studies have now clearly established that the diverse members of the human family of small HSPs (HSPB1-HSPB10) play crucial roles in a wide range of cell types to maintain the integrity and function of tissues, in particular that of nervous and muscular tissue. The 10 human HSPBs clearly have overlapping and non-overlapping functional characteristics. Their ability to self- and hetero-oligomerise provides the cells with a large array of potentially different, specific functions. Single HSPB members can have a multitude of functions (moonlighting) and act on different "clients", thus affecting a wide range of different processes or structures that can ultimately affect the rate of aging of tissues and entire organisms. This is underscored by the findings that some inherited diseases involve mutations in several HSPB members that cause premature (mostly muscle and neuronal) tissue degeneration. Inversely, cancer cell resistance to different anticancer therapies is associated with elevated expression of several HSPBs. Still, many unanswered questions exist about the precise functioning of HSPBs, their collaboration with other HSPB members as well as their functions within the entire cellular chaperone network. Also, better insight in the regulation of expression of the various members and how their function is modulated post-translationally is needed. Such may be crucially important to develop means to intervene with their function for therapeutic purposes, which would require functional down-regulation in cancer but up-regulation in, for instance, cardiac or degenerative neuro/neuromuscular diseases. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology.
尽管最初有些被忽视，但最近的研究已经清楚地表明，人类小 HSP 家族（HSPB1-HSPB10）的多样化成员在广泛的细胞类型中发挥着至关重要的作用，以维持组织的完整性和功能，特别是神经和肌肉组织。这 10 种人类 HSPB 显然具有重叠和非重叠的功能特征。它们自我和异源寡聚化的能力为细胞提供了大量潜在不同的、特定的功能。单个 HSPB 成员可以具有多种功能（兼职），并作用于不同的“客户”，从而影响广泛的不同过程或结构，最终影响组织和整个生物体的衰老速度。一些遗传性疾病涉及多个 HSPB 成员的突变，导致组织过早（主要是肌肉和神经元）退化，这突出了这一点。相反，癌细胞对不同抗癌疗法的耐药性与几种 HSPB 的高表达有关。尽管如此，关于 HSPB 的精确功能、它们与其他 HSPB 成员的协作以及它们在整个细胞伴侣网络中的功能，仍然存在许多未解答的问题。还需要更好地了解各种成员的表达调控及其功能如何在翻译后被调节。这对于开发干预其功能的治疗方法可能至关重要，这在癌症中需要功能下调，但在心脏或退行性神经/神经肌肉疾病中需要功能上调。本文是一个专题题为“小 HSP 在生理和病理中的作用”的一部分。
