Shibata Yoko, Morimoto Richard I
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Curr Biol. 2014 May 19;24(10):R463-74. doi: 10.1016/j.cub.2014.03.033.
The proper folding of proteins is continuously challenged by intrinsic and extrinsic stresses, and the accumulation of toxic misfolded proteins is associated with many human diseases. Eukaryotic cells have evolved a complex network of protein quality control pathways to protect the proteome, and these pathways are specialized for each subcellular compartment. While many details have been elucidated for how the cytosol and endoplasmic reticulum counteract proteotoxic stress, relatively little is known about the pathways protecting the nucleus from protein misfolding. Proper maintenance of nuclear proteostasis has important implications in preserving genomic integrity, as well as for aging and disease. Here, we offer a conceptual framework for how proteostasis is maintained in this organelle. We define the particular requirements that must be considered for the nucleus to manage proteotoxic stress, summarize the known and implicated pathways of nuclear protein quality control, and identify the unresolved questions in the field.
蛋白质的正确折叠不断受到内在和外在压力的挑战，有毒错误折叠蛋白质的积累与许多人类疾病相关。真核细胞进化出了一个复杂的蛋白质质量控制途径网络来保护蛋白质组，并且这些途径针对每个亚细胞区室具有特异性。虽然关于细胞质和内质网如何对抗蛋白质毒性应激已经阐明了许多细节，但对于保护细胞核免受蛋白质错误折叠的途径了解相对较少。核蛋白质稳态的适当维持对于保持基因组完整性以及衰老和疾病具有重要意义。在这里，我们提供了一个关于该细胞器中蛋白质稳态如何维持的概念框架。我们定义了细胞核应对蛋白质毒性应激必须考虑的特定要求，总结了已知的和涉及的核蛋白质质量控制途径，并确定了该领域尚未解决的问题。
