Department of Biochemistry and Molecular Medicine, School of Medicine, West Virginia University, 64 Medical Center Drive, Morgantown, WV 26506, USA.
Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA.
Biomolecules. 2023 Aug 29;13(9):1326. doi: 10.3390/biom13091326.
The proteasome, a complex multi-catalytic protease machinery, orchestrates the protein degradation essential for maintaining cellular homeostasis, and its dysregulation also underlies many different types of diseases. Its function is regulated by many different mechanisms that encompass various factors such as proteasome activators (PAs), adaptor proteins, and post-translational modifications. This review highlights the unique characteristics of proteasomal regulation through the lens of a distinct family of regulators, the 11S, REGs, or PA26/PA28. This ATP-independent family, spanning from amoebas to mammals, exhibits a common architectural structure; yet, their cellular biology and criteria for protein degradation remain mostly elusive. We delve into their evolution and cellular biology, and contrast their structure and function comprehensively, emphasizing the unanswered questions regarding their regulatory mechanisms and broader roles in proteostasis. A deeper understanding of these processes will illuminate the roles of this regulatory family in biology and disease, thus contributing to the advancement of therapeutic strategies.
蛋白酶体是一种复杂的多催化蛋白酶机制，它协调着蛋白质降解，这对维持细胞内环境稳定至关重要，其失调也与许多不同类型的疾病有关。其功能受到许多不同机制的调节，这些机制包含各种因素，如蛋白酶体激活剂（PAs）、衔接蛋白和翻译后修饰。本综述通过一个独特的调节因子家族——11S、REGs 或 PA26/PA28——的视角来突出蛋白酶体调节的独特特征。这个从变形虫到哺乳动物的非 ATP 依赖性家族具有共同的结构；然而，它们的细胞生物学和蛋白质降解标准在很大程度上仍不清楚。我们深入研究了它们的进化和细胞生物学，并全面对比了它们的结构和功能，强调了关于它们的调节机制和在蛋白质稳态中的更广泛作用的未解决问题。对这些过程的深入了解将阐明这个调节家族在生物学和疾病中的作用，从而为治疗策略的发展做出贡献。
