Arrieta Adrian, Vondriska Thomas M
Departments of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Departments of Medicine/Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Front Mol Biosci. 2022 Sep 30;9:990006. doi: 10.3389/fmolb.2022.990006. eCollection 2022.
Maintenance of protein folding homeostasis, or proteostasis is critical for cell survival as well as for execution of cell type specific biological processes such as muscle cell contractility, neuronal synapse and memory formation, and cell transition from a mitotic to post-mitotic cell type. Cell type specification is driven largely by chromatin organization, which dictates which genes are turned off or on, depending on cell needs and function. Loss of chromatin organization can have catastrophic consequences either on cell survival or cell type specific function. Chromatin organization is highly dependent on organization of nucleosomes, spatiotemporal nucleosome assembly and disassembly, and histone turnover. In this review our goal is to highlight why nucleosome proteostasis is critical for chromatin organization, how this process is mediated by histone chaperones and ATP-dependent chromatin remodelers and outline potential and established mechanisms of disrupted nucleosome proteostasis during disease. Finally, we highlight how these mechanisms of histone turnover and nucleosome proteostasis may conspire with unfolded protein response programs to drive histone turnover in cell growth and development.
维持蛋白质折叠稳态，即蛋白质稳态，对于细胞存活以及执行特定细胞类型的生物学过程至关重要，例如肌肉细胞收缩、神经元突触和记忆形成，以及细胞从有丝分裂细胞类型向有丝分裂后细胞类型的转变。细胞类型特异性很大程度上由染色质组织驱动，染色质组织根据细胞需求和功能决定哪些基因关闭或开启。染色质组织的丧失可能对细胞存活或细胞类型特异性功能产生灾难性后果。染色质组织高度依赖于核小体的组织、核小体的时空组装和解聚以及组蛋白周转。在本综述中，我们的目标是强调为什么核小体蛋白质稳态对染色质组织至关重要，该过程如何由组蛋白伴侣和ATP依赖的染色质重塑因子介导，并概述疾病期间核小体蛋白质稳态破坏的潜在机制和已确定机制。最后，我们强调组蛋白周转和核小体蛋白质稳态的这些机制如何与未折叠蛋白反应程序共同作用，以驱动细胞生长和发育过程中的组蛋白周转。
