期刊
EMBO JOURNAL
卷 33, 期 21, 页码 2492-2506出版社
WILEY
DOI: 10.15252/embj.201488208
关键词
E3 ubiquitin-protein ligase; GxGD intramembrane protease; protein homeostasis; rhomboid pseudoprotease
资金
- Baden-Wurttemberg Stiftung within the Network of Aging Research (NAR, University of Heidelberg)
- Deutsche Forschungsgemeinschaft [SFB 1036, TP 12]
- Boehringer Ingelheim Fonds
Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of signal peptides at the endoplasmic reticulum (ER), but has also been suggested to play a role in ER-associated degradation (ERAD). Here, we show that SPP forms a complex with the ERAD factor Derlin1 and the E3 ubiquitin ligase TRC8 to cleave the unfolded protein response (UPR) regulator XBP1u. Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. Additionally, Derlin1 acts in the complex as a substrate receptor by recognizing the luminal tail of XBP1u. Remarkably, this interaction of Derlin1 with XBP1u obviates the need for ectodomain shedding prior to SPP cleavage, commonly required for intramembrane cuts. Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. Thus, we identify an ERAD complex that controls the abundance of XBP1u and thereby tunes signaling through the UPR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据