Parkin Mono-ubiquitinates Bcl-2 and Regulates Autophagy
Parkin Mono-ubiquitinates Bcl-2 and Regulates Autophagy
复制标题
Parkin 单泛素化 BCL-2 并调节自噬
DOI：
10.1074/jbc.m110.101469
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发表时间：
2010-12-03
影响因子：
4.8
通讯作者：
Wang, Guanghui
中科院分区：
文献类型：
--
作者：
Chen, Dong;Gao, Feng;Wang, Guanghui
Parkin是一种E3泛素连接酶，介导蛋白质底物的泛素化。Parkin基因的突变可导致parkin功能丧失，并导致常染色体隐性遗传性青少年帕金森综合征。最近，有报道称parkin参与了吞丝分裂的调节。在这里，我们确定了抗凋亡和自噬抑制蛋白Bcl-2作为parkin的底物。Parkin通过其C端直接与Bcl2结合，介导Bcl2的单一泛素化，从而增加Bcl2的稳态水平。Parkin的过度表达，但不是其连接酶缺陷形式，降低了自噬标记LC3的转换，而敲除parkin则增加了LC3II的水平。在缺乏parkin的HeLa细胞中，parkin的敲除不会改变Lc3的转化。此外，Parkin的过表达增强了Bcl2和Beclin 1之间的相互作用。我们的结果为Parkin单泛素化Bcl2并通过Bcl2调节自噬提供了证据。
Parkin is an E3 ubiquitin ligase that mediates the ubiquitination of protein substrates. The mutations in the parkin gene can lead to a loss of function of parkin and cause autosomal recessive juvenile onset parkinsonism. Recently, parkin was reported to be involved in the regulation of mitophagy. Here, we identify the Bcl-2, an anti-apoptotic and autophagy inhibitory protein, as a substrate for parkin. Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. Overexpression of parkin, but not its ligase-deficient forms, decreases autophagy marker LC3 conversion, whereas knockdown of parkin increases LC3 II levels. In HeLa cells, a parkin-deficient cell line, knockdown of parkin does not change LC3 conversion. Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2.