Arrigo André-Patrick
Laboratoire stress oxydant, chaperons et apoptose, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon-1, Villeurbanne, France.
Med Sci (Paris). 2005 Jun-Jul;21(6-7):619-25. doi: 10.1051/medsci/2005216-7619.
Exposure to different conditions or agents that destabilize cell homeostasis often alters protein folding. Depending on stress intensity irreversible protein aggregation and cell death can occur. Cells have developed a conserved defense mechanism aimed at reducing the deleterious effects induced by protein folding alteration. This mechanism is characterized by the expression of a small number of genes encoding specific proteins, named Hsps. Several of these proteins act as molecular chaperones through their ability to refold polypeptides with an altered conformation. Moreover, constitutive Hsps homologues have been characterized that participate in the folding of newly made polypeptides, in the assembly of protein complexes in the endoplasmic reticulum, in the translocation of polypeptides through membranes or in masking mutations that alter protein folding. Neurodegeneratives and cancereous diseases are discussed as examples where high levels of Hsp expression can be either beneficial or deleterious to the cells.
暴露于破坏细胞稳态的不同条件或因子下，常常会改变蛋白质折叠。根据应激强度的不同，可能会发生不可逆的蛋白质聚集和细胞死亡。细胞已形成一种保守的防御机制，旨在减少蛋白质折叠改变所诱导的有害影响。这种机制的特点是表达少数编码特定蛋白质（即热休克蛋白，Hsps）的基因。其中一些蛋白质通过重新折叠构象改变的多肽的能力，充当分子伴侣。此外，组成型Hsps同源物也已得到鉴定，它们参与新生多肽的折叠、内质网中蛋白质复合物的组装、多肽通过膜的转运或掩盖改变蛋白质折叠的突变。文中以神经退行性疾病和癌症为例，探讨了高水平Hsp表达对细胞可能有益或有害的情况。
