Substrate receptors of proteasomes
Substrate receptors of proteasomes
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蛋白酶体的底物受体
DOI：
10.1111/brv.12419
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发表时间：
2018-11-01
影响因子：
10
通讯作者：
Qiu, Xiao-Bo
中科院分区：
文献类型：
--
作者：
Jiang, Tian-Xia;Zhao, Mei;Qiu, Xiao-Bo
蛋白酶体负责大多数细胞蛋白质的周转，因此对几乎所有的细胞活动都是至关重要的。进入蛋白酶体的底物必须首先与底物受体结合。底物受体可分为泛素受体和非泛素受体。固有的泛素受体，包括蛋白酶体调节颗粒碱基亚基1、10和13(Rpn1、Rpn10和Rpn13)，决定了蛋白酶体识别泛素链的能力，从而为26S蛋白酶体提供了选择性。然而，非泛素受体，包括蛋白酶体激活剂2 0 0(PA2 0 0)和PA2 8γ，由于其相对于典型的泛素介导的蛋白酶体降解具有显著的代偿作用而受到广泛关注。在此，我们综述了这些底物受体在蛋白酶体降解中作用的最新进展，并介绍了它们的底物和相互作用的因素。我们还提供了与精子发生、免疫反应、细胞动态平衡和肿瘤发展相关的生物学功能的见解。最后，我们总结了这些底物受体的小分子抑制剂的开发进展，并讨论了它们作为药物靶点的潜力。
Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non‐ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome. However, the non‐ubiquitin receptors, including proteasome activator 200 (PA200) and PA28γ, have received great attention due to their remarkable compensatory roles relative to canonical ubiquitin‐mediated proteasomal degradation. Herein we review recent advances in understanding the contributions of these substrate receptors to proteasomal degradation, and introduce their substrates and interacting factors. We also provide insights into their biological functions related to spermatogenesis, immune responses, cellular homeostasis, and tumour development. Finally, we summarize advances in developing small‐molecule inhibitors of these substrate receptors and discuss their potential as drug targets.