Fernández-Fernández María Rosario, Gragera Marcos, Ochoa-Ibarrola Lissette, Quintana-Gallardo Lucía, Valpuesta José María
Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
FEBS Lett. 2017 Sep;591(17):2648-2660. doi: 10.1002/1873-3468.12751. Epub 2017 Jul 25.
Proteostasis, the controlled balance of protein synthesis, folding, assembly, trafficking and degradation, is a paramount necessity for cell homeostasis. Impaired proteostasis is a hallmark of ageing and of many human diseases. Molecular chaperones are essential for proteostasis in eukaryotic cells, and their function has traditionally been linked to protein folding, assembly and disaggregation. More recent findings suggest that chaperones also contribute to key steps in protein degradation. In particular, Hsp70 has an essential role in substrate degradation through the ubiquitin-proteasome system, as well as through different autophagy pathways. Accumulated knowledge suggests that the fate of an Hsp70 substrate is dictated by the combination of partners (cochaperones and other chaperones) that interact with Hsp70 in a given cell context.
蛋白质稳态是蛋白质合成、折叠、组装、运输和降解的可控平衡，对于细胞稳态至关重要。蛋白质稳态受损是衰老和许多人类疾病的标志。分子伴侣对于真核细胞中的蛋白质稳态至关重要，其功能传统上与蛋白质折叠、组装和解聚有关。最近的研究结果表明，分子伴侣也有助于蛋白质降解的关键步骤。特别是，热休克蛋白70（Hsp70）在通过泛素-蛋白酶体系统以及不同的自噬途径进行的底物降解中起着至关重要的作用。积累的知识表明，Hsp70底物的命运取决于在特定细胞环境中与Hsp70相互作用的伴侣（共伴侣和其他分子伴侣）的组合。
