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Cue1p中的一个泛素结合酶7(Ubc7p)结合结构域激活内质网相关蛋白降解。

A Ubc7p-binding domain in Cue1p activates ER-associated protein degradation.

作者信息

Kostova Zlatka, Mariano Jennifer, Scholz Simone, Koenig Carolin, Weissman Allan M

机构信息

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

出版信息

J Cell Sci. 2009 May 1;122(Pt 9):1374-81. doi: 10.1242/jcs.044255. Epub 2009 Apr 14.

Abstract

Cue1p is an N-terminally anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). Cue1p contains a CUE domain, which for several proteins is known to bind ubiquitin. We now establish that the CUE domain is dispensable for ERAD of substrates of both Hrd1p and Doa10p and that the Cue1p transmembrane domain is similarly not required for degradation of the Hrd1p substrate CPY. Cue1p interacts with the ERAD E2 Ubc7p in vivo. We show that a discrete C-terminal Ubc7p binding region (U7BR) of Cue1p is required for ERAD and for Ubc7p-dependent ubiquitylation by Hrd1p in vitro. Strikingly, when Ubc7p is stabilized by direct anchoring to the ER membrane, the U7BR is sufficient to restore ERAD in cells lacking Cue1p. Thus, discrete E2 binding sites independent of ubiquitin ligase domains have the potential to activate ubiquitylation.

摘要

Cue1p是一种N端锚定的内质网(ER)蛋白,对于参与内质网相关降解(ERAD)的两种主要酵母RING指型泛素连接酶(E3)的活性至关重要。Cue1p包含一个CUE结构域,已知该结构域可与多种蛋白质结合泛素。我们现在确定,CUE结构域对于Hrd1p和Doa10p底物的ERAD并非必需,并且Cue1p跨膜结构域对于Hrd1p底物CPY的降解同样不是必需的。Cue1p在体内与ERAD E2 Ubc7p相互作用。我们表明,Cue1p的一个离散的C端Ubc7p结合区域(U7BR)对于ERAD以及体外Hrd1p介导的Ubc7p依赖性泛素化是必需的。令人惊讶的是,当Ubc7p通过直接锚定在内质网膜上而稳定时,U7BR足以在缺乏Cue1p的细胞中恢复ERAD。因此,独立于泛素连接酶结构域的离散E2结合位点具有激活泛素化的潜力。

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