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| Open AccessRHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling
Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.
- Julia D. Knopf
- , Susanne S. Steigleder
- & Marius K. Lemberg
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Article
| Open AccessSEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex
The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.
- Liangguang Leo Lin
- , Huilun Helen Wang
- & Ling Qi
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Article
| Open AccessDirect observation of autoubiquitination for an integral membrane ubiquitin ligase in ERAD
The stoichiometry of Hrd1, an integral membrane E3 ubiquitin ligase is critical to maintaining proteostasis in the endoplasmic reticulum. Here, the authors establish a single-molecule counting approach coupled with a single-molecule in vitro ubiquitination system to determine the functional stoichiometry of Hrd1.
- Basila Moochickal Assainar
- , Kaushik Ragunathan
- & Ryan D. Baldridge
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Article
| Open AccessProteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis
The nature of SEL1L-HRD1 ERAD substrates remains unclear. Here, the authors identified ~100 endogenous substrates, and showed that SEL1L-HRD1 ERAD is indispensable for the activity of GPI transamidase complex and the biogenesis of GPI-anchored proteins.
- Xiaoqiong Wei
- , You Lu
- & Ling Qi
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Article
| Open AccessA slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain
Glycoprotein US9 of human cytomegalovirus downregulates the activating immune ligand MICA*008 to avoid NK cell activation. Here, Seidel et al. show that the signal peptide of US9 is cleaved unusually slowly, causing MICA*008 to be retained in the endoplasmic reticulum (ER) and degraded via the ER quality control system.
- Einat Seidel
- , Liat Dassa
- & Ofer Mandelboim
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Article
| Open AccessCross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation
Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.
- Yicheng Wang
- , Yusuke Maeda
- & Taroh Kinoshita
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Article
| Open AccessUfd2p synthesizes branched ubiquitin chains to promote the degradation of substrates modified with atypical chains
How ubiquitination affects the proteins it modifies varies according to the type of linkage between ubiquitin moieties. Here, Liuet al. show how yeast Udf2p promotes K48 linkage formation onto K29-linked chains to generate branched K29-K48 ubiquitin chains that target its substrate to the proteasome.
- Chao Liu
- , Weixiao Liu
- & Wei Li
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Article
| Open AccessQuantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers
The AAA+ ATPase p97 is an essential hexameric protein with multiple protein interaction partners and cellular functions. Here, the authors use interaction mapping to examine partner proteins of this large complex, and assess the effects of these proteins on the disassembly of the p97 complex.
- Anup Arumughan
- , Yvette Roske
- & Erich E. Wanker
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Article
| Open AccessTRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis
A cellular protease, SPP, participates in production of the mature core protein of hepatitis C virus (HCV). Here, the authors show in mouse models that SPP inhibition reduces viral propagation and pathogenesis via proteasomal degradation of the immature core protein mediated by the E3 ubiquitin ligase TRC8.
- Sayaka Aizawa
- , Toru Okamoto
- & Yoshiharu Matsuura
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Article
| Open AccessA high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation
The human cytomegalovirus protein US11 downregulates host immune responses by redirecting HLA class I molecules for endoplasmic reticulum-associated protein degradation. Using a high-coverage genome-wide shRNA screen, the authors identify TMEM129 as an E3 ubiquitin ligase essential for this process.
- Michael L. van de Weijer
- , Michael C. Bassik
- & Robert Jan Lebbink
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Article |
TorsinA participates in endoplasmic reticulum-associated degradation
The torsinA protein localizes to the endoplasmic reticulum and, when mutated, causes early onset torsion dystonia. The authors reveal a new role for torsinA in proteosome-mediated degradation of misfolded proteins, and relate this to endoplasmic reticulum stress, in aCaenorhabditis elegansmodel and patient fibroblasts.
- Flávia C. Nery
- , Ioanna A. Armata
- & Xandra O. Breakefield