Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination.
Parkin mediates apparent E2-independent monoubiquitination in vitro and contains an intrinsic activity that catalyzes polyubiquitination.
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DOI：
10.1371/journal.pone.0019720
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lim KL
中科院分区：
文献类型：
--
作者：
Chew KC;Matsuda N;Saisho K;Lim GG;Chai C;Tan HM;Tanaka K;Lim KL
编码泛素连接酶 (E3) 的 Parkin 基因突变是常染色体隐性遗传帕金森病的主要原因。尽管 Parkin 介导的泛素化最初与蛋白质降解有关，但越来越多的证据表明，该酶能够催化多种形式的泛素修饰，包括单泛素化、K48 和 K63 连接的多泛素化。在这项研究中，我们试图了解单一酶如何表现出如此多功能的催化特性。通过体外泛素化测定结合质谱分析，我们惊讶地发现parkin显然能够在体外介导不依赖于E2的蛋白质泛素化，这是E3成员表现出的前所未有的活性。有趣的是，全长parkin仅催化单泛素化，无论E2是否存在，而仅含有催化部分的截短parkin突变体支持E2独立和E2依赖性泛素链组装。我们的结果表明parkin活性的复杂调节，可能有助于解释像parkin这样的单一酶如何介导多种形式的泛素化。
Mutations in the parkin gene, which encodes a ubiquitin ligase (E3), are a major cause of autosomal recessive parkinsonism. Although parkin-mediated ubiquitination was initially linked to protein degradation, accumulating evidence suggests that the enzyme is capable of catalyzing multiple forms of ubiquitin modifications including monoubiquitination, K48- and K63-linked polyubiquitination. In this study, we sought to understand how a single enzyme could exhibit such multifunctional catalytic properties. By means of in vitro ubiquitination assays coupled with mass spectrometry analysis, we were surprised to find that parkin is apparently capable of mediating E2-independent protein ubiquitination in vitro, an unprecedented activity exhibited by an E3 member. Interestingly, whereas full length parkin catalyzes solely monoubiquitination regardless of the presence or absence of E2, a truncated parkin mutant containing only the catalytic moiety supports both E2-independent and E2-dependent assembly of ubiquitin chains. Our results here suggest a complex regulation of parkin's activity and may help to explain how a single enzyme like parkin could mediate diverse forms of ubiquitination.
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DOI：
10.1083/jcb.200611128
发表时间：
2007-09-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Olzmann JA;Li L;Chudaev MV;Chen J;Perez FA;Palmiter RD;Chin LS
通讯作者：
Chin LS
影响因子：
64.8
作者：
Li, Wei;Tu, Daqi;Ye, Yihong
通讯作者：
Ye, Yihong
DOI：
10.1083/jcb.200910140
发表时间：
2010-04-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Matsuda N;Sato S;Shiba K;Okatsu K;Saisho K;Gautier CA;Sou YS;Saiki S;Kawajiri S;Sato F;Kimura M;Komatsu M;Hattori N;Tanaka K
通讯作者：
Tanaka K
Parkin对泛素 - 蛋白酶体系统的广泛激活对于线粒体至关重要。
影响因子：
3.5
作者：
Chan NC;Salazar AM;Pham AH;Sweredoski MJ;Kolawa NJ;Graham RL;Hess S;Chan DC
通讯作者：
Chan DC
DOI：
10.1083/jcb.200809125
发表时间：
2008-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Narendra D;Tanaka A;Suen DF;Youle RJ
通讯作者：
Youle RJ