Almendáriz-Palacios Carla, Gillespie Zoe E, Janzen Matthew, Martinez Valeria, Bridger Joanna M, Harkness Troy A A, Mousseau Darrell D, Eskiw Christopher H
Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada.
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada.
Biomedicines. 2020 Jul 1;8(7):188. doi: 10.3390/biomedicines8070188.
Cellular health is reliant on proteostasis-the maintenance of protein levels regulated through multiple pathways modulating protein synthesis, degradation and clearance. Loss of proteostasis results in serious disease and is associated with aging. One proteinaceous structure underlying the nuclear envelope-the nuclear lamina-coordinates essential processes including DNA repair, genome organization and epigenetic and transcriptional regulation. Loss of proteostasis within the nuclear lamina results in the accumulation of proteins, disrupting these essential functions, either via direct interactions of protein aggregates within the lamina or by altering systems that maintain lamina structure. Here we discuss the links between proteostasis and disease of the nuclear lamina, as well as how manipulating specific proteostatic pathways involved in protein clearance could improve cellular health and prevent/reverse disease.
细胞健康依赖于蛋白质稳态——通过调节蛋白质合成、降解和清除的多种途径维持蛋白质水平。蛋白质稳态的丧失会导致严重疾病，并与衰老相关。核膜下的一种蛋白质结构——核纤层——协调包括DNA修复、基因组组织以及表观遗传和转录调控在内的重要过程。核纤层内蛋白质稳态的丧失会导致蛋白质积累，通过核纤层内蛋白质聚集体的直接相互作用或改变维持核纤层结构的系统，破坏这些重要功能。在这里，我们讨论蛋白质稳态与核纤层疾病之间的联系，以及操纵参与蛋白质清除的特定蛋白质稳态途径如何改善细胞健康并预防/逆转疾病。
