TP53INP2 mediates autophagic degradation of ubiquitinated proteins through its ubiquitin-interacting motif
TP53INP2 mediates autophagic degradation of ubiquitinated proteins through its ubiquitin-interacting motif
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TP53INP2 通过其泛素相互作用基序介导泛素化蛋白的自噬降解
DOI：
10.1002/1873-3468.13467
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发表时间：
2019-08-01
期刊：
影响因子：
3.5
通讯作者：
Wan, Wei
中科院分区：
文献类型：
--
作者：
Xu, Yinfeng;Wan, Wei
据报道，肿瘤蛋白p53诱导核蛋白2（TP53INP2）通过与自噬体定位的自噬相关蛋白8（Atg 8）家族蛋白（包括LC 3）相互作用而参与自噬。在这里，我们发现了TP53 INP2在蛋白质自噬降解中的新功能。我们鉴定了TP53 INP2的泛素相互作用基序（UIM），该基序介导其与泛素和泛素化蛋白的结合。缺乏UIM的TP53INP2能够从LC 3置换自噬接头p62，这导致细胞中泛素化蛋白的积累。此外，缺乏UIM的TP53 INP2的过表达使细胞对氯喹处理敏感。我们的研究结果表明，TP53 INP2可能作为一种新的自噬适配器，通过招募泛素化底物的自噬体降解。
The tumor protein p53-inducible nuclear protein 2 (TP53INP2) has been reported to participate in autophagy by interacting with autophagosome-localized autophagy-related protein 8 (Atg8) family proteins, including LC3. Here, we uncover a novel function for TP53INP2 in the autophagic degradation of proteins. We identify the ubiquitin-interacting motif (UIM) of TP53INP2 that mediates its binding to ubiquitin and ubiquitinated proteins. TP53INP2 lacking the UIM is able to displace autophagic adaptor p62 from LC3, which leads to accumulation of ubiquitinated proteins in cells. Furthermore, overexpression of TP53INP2 lacking the UIM sensitizes cells to chloroquine treatment. Our findings indicate that TP53INP2 may act as a novel autophagic adaptor through recruiting ubquitinated substrates to autophagosomes for degradation.