CKIP-1 将 Smurf1 泛素连接酶与蛋白酶体的 Rpt6 亚基偶联，以促进底物降解。
CKIP-1 couples Smurf1 ubiquitin ligase with Rpt6 subunit of proteasome to promote substrate degradation.
机构信息
State Key Laboratory of Proteomics, Department of Genomics and Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
出版信息
EMBO Rep. 2012 Nov 6;13(11):1004-11. doi: 10.1038/embor.2012.144. Epub 2012 Oct 2.
Abstract
CKIP-1 is an activator of the Smurf1 ubiquitin ligase acting to promote the ubiquitylation of Smad5 and MEKK2. The mechanisms involved in the recognition and degradation of these substrates by the proteasome remain unclear. Here, we show that CKIP-1, through its leucine zipper, interacts directly with the Rpt6 ATPase of the 19S regulatory particle of the proteasome. CKIP-1 mediates the Smurf1-Rpt6 interaction and delivers the ubiquitylated substrates to the proteasome. Depletion of CKIP-1 reduces the degradation of Smurf1 and its substrates by Rpt6. These findings reveal an unexpected adaptor role of CKIP-1 in coupling the ubiquitin ligase and the proteasome.
摘要
CKIP-1 是 Smurf1 泛素连接酶的激活剂，可促进 Smad5 和 MEKK2 的泛素化。蛋白酶体识别和降解这些底物的机制仍不清楚。在这里，我们发现 CKIP-1 通过其亮氨酸拉链与蛋白酶体 19S 调节颗粒的 Rpt6 ATP 酶直接相互作用。CKIP-1 介导 Smurf1-Rpt6 相互作用，并将泛素化的底物递送到蛋白酶体。CKIP-1 的耗竭减少了 Rpt6 对 Smurf1 及其底物的降解。这些发现揭示了 CKIP-1 在连接泛素连接酶和蛋白酶体中的一个意外衔接作用。
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