Usa1 Functions as a Scaffold of the HRD-Ubiquitin Ligase

被引：107

作者：

Horn, Sabine C. ^{[1
]}

Hanna, Jennifer ^{[1
]}

Hirsch, Christian ^{[1
]}

Volkwein, Corinna ^{[1
]}

Schuetz, Anja ^{[1
]}

Heinemann, Udo ^{[1
]}

Sommer, Thomas ^{[1
]}

Jarosch, Ernst ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

来源：

MOLECULAR CELL | 2009年 / 36卷 / 05期

关键词：

RETICULUM-ASSOCIATED DEGRADATION; ER-ASSOCIATED DEGRADATION; UNFOLDED-PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEIN; SACCHAROMYCES-CEREVISIAE; QUALITY-CONTROL; MISFOLDED PROTEINS; COMPLEX; YEAST;

D O I：

10.1016/j.molcel.2009.10.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein quality control in the endoplasmic reticulum is of central importance for cellular homeostasis in eukaryotes. Crucial for this process is the HRD-ubiquitin ligase (HMG-CoA reductase degradation), which singles out terminally misfolded proteins and routes them for degradation to cytoplasmic 26S-proteasomes. Certain functions of this enzyme complex are allocated to defined subunits. However, it remains unclear how these components act in a concerted manner. Here, we show that Usa1 functions as a major scaffold protein of the HRD-ligase. For the turnover of soluble substrates, Der1 binding to the C terminus of Usa1 is required. The N terminus of Usa1 associates with Hrd1 and thus bridges Der1 to Hrd1. Strikingly, the Usa1 N terminus also induces oligomerization of the HRD complex, which is an exclusive prerequisite for the degradation of membrane proteins. Our data demonstrate that scaffold proteins are required to adapt ubiquitin ligase activities toward different classes of substrates.

引用

页码：782 / 793

页数：12

共 46 条

[41] The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp [J].