Kors Suzan, Geijtenbeek Karlijne, Reits Eric, Schipper-Krom Sabine
Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Front Mol Biosci. 2019 Jul 16;6:48. doi: 10.3389/fmolb.2019.00048. eCollection 2019.
Intracellular protein synthesis, folding, and degradation are tightly controlled processes to ensure proper protein homeostasis. The proteasome is responsible for the degradation of the majority of intracellular proteins, which are often targeted for degradation via polyubiquitination. However, the degradation rate of proteins is also affected by the capacity of proteasomes to recognize and degrade these substrate proteins. This capacity is regulated by a variety of proteasome modulations including (1) changes in complex composition, (2) post-translational modifications, and (3) altered transcription of proteasomal subunits and activators. Various diseases are linked to proteasome modulation and altered proteasome function. A better understanding of these modulations may offer new perspectives for therapeutic intervention. Here we present an overview of these three proteasome modulating mechanisms to give better insight into the diversity of proteasomes.
细胞内蛋白质的合成、折叠和降解是受到严格控制的过程,以确保适当的蛋白质稳态。蛋白酶体负责大多数细胞内蛋白质的降解,这些蛋白质通常通过多聚泛素化被靶向降解。然而,蛋白质的降解速率也受蛋白酶体识别和降解这些底物蛋白能力的影响。这种能力受到多种蛋白酶体调节的调控,包括:(1)复合物组成的变化;(2)翻译后修饰;(3)蛋白酶体亚基和激活剂转录的改变。多种疾病与蛋白酶体调节和蛋白酶体功能改变有关。对这些调节的更好理解可能为治疗干预提供新的视角。在此,我们概述这三种蛋白酶体调节机制,以更深入了解蛋白酶体的多样性。