Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Department of Bioscience, University of Science and Technology, Daejeon, South Korea.
Exp Mol Med. 2024 Oct;56(10):2127-2144. doi: 10.1038/s12276-024-01329-5. Epub 2024 Oct 11.
Histone lysine methylation is pivotal in shaping the epigenetic landscape and is linked to cell physiology. Coordination of the activities of multiple histone lysine methylation modifiers, namely, methyltransferases and demethylases, modulates chromatin structure and dynamically alters the epigenetic landscape, orchestrating almost all DNA-templated processes, such as transcription, DNA replication, and DNA repair. The stability of modifier proteins, which is regulated by protein degradation, is crucial for their activity. Here, we review the current knowledge of modifier-protein degradation via specific pathways and its subsequent impact on cell physiology through epigenetic changes. By summarizing the functional links between the aberrant stability of modifier proteins and human diseases and highlighting efforts to target protein stability for therapeutic purposes, we aim to promote interest in defining novel pathways that regulate the degradation of modifiers and ultimately increase the potential for the development of novel therapeutic strategies.
组蛋白赖氨酸甲基化在塑造表观遗传景观中起着关键作用，与细胞生理学有关。多种组蛋白赖氨酸甲基化修饰酶（即甲基转移酶和去甲基酶）的活性协调作用，调节染色质结构并动态改变表观遗传景观，协调几乎所有基于 DNA 的过程，如转录、DNA 复制和 DNA 修复。修饰蛋白的稳定性受蛋白降解调控，这对其活性至关重要。在这里，我们通过特定途径综述了修饰蛋白降解的最新知识，以及其通过表观遗传变化对细胞生理学的后续影响。通过总结修饰蛋白稳定性异常与人类疾病之间的功能联系，并强调靶向蛋白稳定性用于治疗目的的努力，我们旨在促进对定义调节修饰物降解的新途径的兴趣，并最终增加开发新治疗策略的潜力。
