Stalled Proteasomes Are Directly Relieved by P97 Recruitment
Stalled Proteasomes Are Directly Relieved by P97 Recruitment
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DOI：
10.1074/jbc.m111.240309
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发表时间：
2011-09-02
影响因子：
4.8
通讯作者：
Stanhill, Ariel
中科院分区：
文献类型：
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作者：
Isakov, Elada;Stanhill, Ariel
26 S蛋白酶体是真核生物中降解大部分细胞蛋白质的蛋白酶.因此，它适应了细胞可能遇到的不同条件下发挥作用的能力。该功能由调节蛋白质降解的各个方面的各种衔接子支持，这些衔接子包括底物递送、去泛素化、解折叠和20 S门扩张的调节。在这里，我们展示了一个新的功能复合物之间的P97和蛋白酶体组装在蛋白酶体损伤。这需要P97通过19 S颗粒与26 S蛋白酶体结合，从而形成额外的六聚体ATP酶环以解除阻遏。P97结合的蛋白酶体显示出对Npl 4-ufd 1 P97辅因子的选择性结合，表明P97结合蛋白酶体的独特细胞作用。P97结合的蛋白酶体显示增强的活性，显示蛋白水解损伤的减轻。我们的研究结果将P97直接置于非ERAD蛋白酶体功能中，并在UPS损伤中建立了一个新的检查点。调节蛋白酶体活性和正确响应蛋白质错误折叠的能力在细胞调节中非常重要。
The 26 S proteasome is the eukaryotic protease responsible for the degradation of most cellular proteins. As such it accommodates the ability to function under diverse conditions that the cell may encounter. This function is supported by various adaptors that modulate various aspects in protein degradation, these include regulation of substrate delivery, deubiquitination, unfolding, and 20 S gate dilation. Here we show a new functional complex between the P97 and the proteasome that is assembled in response to proteasomal impairment. This entails P97 binding to the 26 S proteasome via the 19 S particle thereby forming an additional hexameric ATPase ring to relieve repression. P97-bound proteasomes showed selective binding toward the Npl4-ufd1 P97 co-factors, indicating a unique cellular role for P97 binding to proteasomes. P97-bound proteasomes display enhanced activity, showing a relief in proteolysis impairment. Our findings place P97 directly in non-ERAD proteasomal functions and establish a new checkpoint in UPS impairment. The ability to modulate proteasome activity and properly respond to protein misfolding, is of great importance in cellular regulation.