Simon Stéphanie, Aissat Abdel, Degrugillier Fanny, Simonneau Benjamin, Fanen Pascale, Arrigo André-Patrick
INSERM, IMRB, Paris Est Creteil University, F-94010 Creteil, France.
Département de Génétique, AP-HP, Henri Mondor Hospital, F-94010 Creteil, France.
Int J Mol Sci. 2021 Apr 20;22(8):4252. doi: 10.3390/ijms22084252.
Human small heat shock proteins are molecular chaperones that regulate fundamental cellular processes in normal and pathological cells. Here, we have reviewed the role played by HspB1, HspB4 and HspB5 in the context of Cystic Fibrosis (CF), a severe monogenic autosomal recessive disease linked to mutations in Cystic Fibrosis Transmembrane conductance Regulator protein (CFTR) some of which trigger its misfolding and rapid degradation, particularly the most frequent one, F508del-CFTR. While HspB1 and HspB4 favor the degradation of CFTR mutants, HspB5 and particularly one of its phosphorylated forms positively enhance the transport at the plasma membrane, stability and function of the CFTR mutant. Moreover, HspB5 molecules stimulate the cellular efficiency of currently used CF therapeutic molecules. Different strategies are suggested to modulate the level of expression or the activity of these small heat shock proteins in view of potential in vivo therapeutic approaches. We then conclude with other small heat shock proteins that should be tested or further studied to improve our knowledge of CFTR processing.
人类小分子热休克蛋白是分子伴侣，可调节正常细胞和病理细胞中的基本细胞过程。本文中，我们综述了HspB1、HspB4和HspB5在囊性纤维化（CF）背景下所起的作用，CF是一种严重的单基因常染色体隐性疾病，与囊性纤维化跨膜传导调节蛋白（CFTR）的突变有关，其中一些突变会引发其错误折叠和快速降解，特别是最常见的一种，即F508del-CFTR。虽然HspB1和HspB4有利于CFTR突变体的降解，但HspB5，尤其是其磷酸化形式之一，可正向增强CFTR突变体在质膜上的转运、稳定性和功能。此外，HspB5分子可提高目前用于CF治疗的分子的细胞效率。鉴于潜在的体内治疗方法，建议采用不同策略来调节这些小分子热休克蛋白的表达水平或活性。然后，我们总结了其他应进行测试或进一步研究的小分子热休克蛋白，以增进我们对CFTR加工过程的了解。
