A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
A Role for NBR1 in Autophagosomal Degradation of Ubiquitinated Substrates
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DOI：
10.1016/j.molcel.2009.01.020
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发表时间：
2009-02-27
期刊：
影响因子：
16
通讯作者：
Johansen, Terje
中科院分区：
文献类型：
--
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
自噬是一种分解代谢过程，其中胞质细胞组分被递送到溶酶体进行降解。最近的研究表明存在特异性受体，如p62，其将泛素化靶点与自噬体降解途径联系起来。在这里，我们表明，NBR1（BRCA1基因1的邻居）是一个自噬受体含有LC 3和泛素（Ub）结合结构域。NIBR1被募集到Ub阳性蛋白聚集体中，并通过自噬降解，这取决于LC3相互作用区（LIR）和LC3家族修饰剂。虽然NBR1和p62相互作用并形成寡聚体，但它们可以独立发挥功能，如在p62缺陷细胞中NBR1的自噬体清除所示。NBR1定位于Ub阳性包涵体的患者肝功能障碍，和NBR1的耗竭废除形成Ub阳性p62体嘌呤霉素治疗后的细胞。我们认为NBR1和p62是选择性自噬体降解泛素化靶点的受体。
Autophagy is a catabolic process where cytosolic cellular components are delivered to the lysosome for degradation. Recent studies have indicated the existence of specific receptors, such as p62, which link ubiquitinated targets to autophagosomal degradation pathways. Here we show that NBR1 (neighbor of BRCA1 gene 1) is an autophagy receptor containing LC3- and ubiquitin (Ub)-binding domains. NIBR1 is recruited to Ub-positive protein aggregates and degraded by autophagy depending on an LC3-interacting region (LIR) and LC3 family modifiers. Although NBR1 and p62 interact and form oligomers, they can function independently, as shown by autophagosomal clearance of NBR1 in p62-deficient cells. NBR1 was localized to Ub-positive inclusions in patients with liver dysfunction, and depletion of NBR1 abolished the formation of Ub-positive p62 bodies upon puromycin treatment of cells. We propose that NBR1 and p62 act as receptors for selective autophagosomal degradation of ubiquitinated targets.