The Ubiquitin Ligase Hul5 Promotes Proteasomal Processivity
The Ubiquitin Ligase Hul5 Promotes Proteasomal Processivity
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DOI：
10.1128/mcb.00909-09
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发表时间：
2010-02-15
影响因子：
5.3
通讯作者：
Kornitzer, Daniel
中科院分区：
文献类型：
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作者：
Aviram, Sharon;Kornitzer, Daniel
26S蛋白酶体是一种大型的细胞质蛋白水解酶，能将多聚泛素化蛋白连续降解为短肽。蛋白酶体19S调控亚复合体通过其多泛素加合物将目标蛋白捆绑在一起，并解开目标多肽，然后将其插入到含有蛋白分解位点的20S亚复合体中。Hul5是一种19S亚复合体相关的泛素连接酶，它在蛋白酶体结合的底物上延长泛素链。我们分离了hul5 Delta作为一种突变，通过这种突变，不稳定的周期蛋白与稳定的报告蛋白的融合会作为部分加工产物积累起来。这些产物在野生型中短暂出现，但在19S ATPase突变体和hul5 Delta突变体中高度稳定，支持ATPase亚单位在蛋白酶体底物插入催化空腔之前展开的作用，并表明Hul5在蛋白酶体上停滞不前的蛋白质的过程中降解。
The 26S proteasome is a large cytoplasmic protease that degrades polyubiquitinated proteins to short peptides in a processive manner. The proteasome 19S regulatory subcomplex tethers the target protein via its polyubiquitin adduct and unfolds the target polypeptide, which is then threaded into the proteolytic site-containing 20S subcomplex. Hul5 is a 19S subcomplex-associated ubiquitin ligase that elongates ubiquitin chains on proteasome-bound substrates. We isolated hul5 Delta as a mutation with which fusions of an unstable cyclin to stable reporter proteins accumulate as partially processed products. These products appear transiently in the wild type but are strongly stabilized in 19S ATPase mutants and in the hul5 Delta mutant, supporting a role for the ATPase subunits in the unfolding of proteasome substrates before insertion into the catalytic cavity and suggesting a role for Hul5 in the processive degradation of proteins that are stalled on the proteasome.