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首页> 外文期刊>Molecular and Cellular Biology >Sequestosome 1/p62 Is a Polyubiquitin Chain Binding Protein Involved in Ubiquitin Proteasome Degradation
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Sequestosome 1/p62 Is a Polyubiquitin Chain Binding Protein Involved in Ubiquitin Proteasome Degradation

机译：Sequestosome 1 / p62是一种泛素链结合蛋白，参与泛素蛋白酶体降解。

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Herein, we demonstrate that the ubiquitin-associated (UBA) domain of sequestosome 1/p62 displays a preference for binding K63-polyubiquitinated substrates. Furthermore, the UBA domain of p62 was necessary for aggregate sequestration and cell survival. However, the inhibition of proteasome function compromised survival in cells with aggregates. Mutational analysis of the UBA domain reveals that the conserved hydrophobic patch MGF as well as the conserved leucine in helix 2 are necessary for binding polyubiquitinated proteins and for sequestration-aggregate formation. We report that p62 interacts with the proteasome by pull-down assay, coimmunoprecipitation, and colocalization. Depletion of p62 levels results in an inhibition of ubiquitin proteasome-mediated degradation and an accumulation of ubiquitinated proteins. Altogether, our results support the hypothesis that p62 may act as a critical ubiquitin chain-targeting factor that shuttles substrates for proteasomal degradation.
机译：在这里，我们证明了螯合物1 / p62的遍在蛋白相关（UBA）域显示出优先结合K63多聚遍在蛋白的底物。此外，p62的UBA结构域对于聚集螯合和细胞存活是必需的。然而，蛋白酶体功能的抑制损害了具有聚集体的细胞的存活。 UBA结构域的突变分析表明，螺旋2中保守的疏水性斑块MGF和保守的亮氨酸对于结合多泛素化蛋白和螯合聚集体形成是必需的。我们报告说p62通过下拉测定，免疫共沉淀和共定位与蛋白酶体相互作用。 p62水平的减少会导致泛素蛋白酶体介导的降解受到抑制以及泛素化蛋白的积累。总而言之，我们的结果支持以下假设：p62可能是关键的泛素链靶向因子，可以使底物穿梭进行蛋白酶体降解。

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