scholarly journals Author response: Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling

2020 ◽  
Author(s):  
Emma J Fenech ◽  
Federica Lari ◽  
Philip D Charles ◽  
Roman Fischer ◽  
Marie Laétitia-Thézénas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Ubiquitin Ligases ◽  
Innate Immune ◽  
Author Response

scholarly journals Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Emma J Fenech ◽  
Federica Lari ◽  
Philip D Charles ◽  
Roman Fischer ◽  
Marie Laétitia-Thézénas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Interactions ◽  
Protein Quality ◽  
Transmembrane Domain ◽  
Ubiquitin Ligases ◽  
Bioinformatic Analysis ◽  
Innate Immune ◽  
Calcium Flux ◽  
Sting Pathway ◽  
Er Membrane

Ubiquitin ligases (E3s) embedded in the endoplasmic reticulum (ER) membrane regulate essential cellular activities including protein quality control, calcium flux, and sterol homeostasis. At least 25 different, transmembrane domain (TMD)-containing E3s are predicted to be ER-localised, but for most their organisation and cellular roles remain poorly defined. Using a comparative proteomic workflow, we mapped over 450 protein-protein interactions for 21 stably expressed, full-length E3s. Bioinformatic analysis linked ER-E3s and their interactors to multiple homeostatic, regulatory, and metabolic pathways. Among these were four membrane-embedded interactors of RNF26, a polytopic E3 whose abundance is auto-regulated by ubiquitin-proteasome dependent degradation. RNF26 co-assembles with TMEM43, ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate immune signalling through the cGAS-STING pathway. This RNF26 complex represents a new modulatory axis of STING and innate immune signalling at the ER membrane. Collectively, these data reveal the broad scope of regulation and differential functionalities mediated by ER-E3s for both membrane-tethered and cytoplasmic processes.

scholarly journals Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling

2020 ◽  
Author(s):  
Emma J. Fenech ◽  
Federica Lari ◽  
Philip D. Charles ◽  
Roman Fischer ◽  
Marie Laétitia-Thézénas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Interactions ◽  
Protein Quality ◽  
Transmembrane Domain ◽  
Ubiquitin Ligases ◽  
Bioinformatic Analysis ◽  
Innate Immune ◽  
Calcium Flux ◽  
Sting Pathway ◽  
Er Membrane

AbstractUbiquitin ligases (E3s) embedded in the endoplasmic reticulum (ER) membrane regulate essential cellular activities including protein quality control, calcium flux, and sterol homeostasis. At least 25 different, transmembrane domain (TMD)-containing E3s are predicted to be ER-localised, but for most their organisation and cellular roles remain poorly defined. Using a comparative proteomic workflow, we mapped over 450 protein-protein interactions for 21 different stably expressed, full-length E3s. Bioinformatic analysis linked ER-E3s and their interactors to multiple homeostatic, regulatory, and metabolic pathways. Among these were four membrane-embedded interactors of RNF26, a polytopic E3 whose abundance is auto-regulated by ubiquitin-proteasome dependent degradation. RNF26 co-assembles with TMEM43, ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate immune signalling through the cGAS-STING pathway. This RNF26 complex represents a new modulatory axis of STING and innate immune signalling at the ER membrane. Collectively, these data reveal the broad scope of regulation and differential functionalities mediated by ER-E3s for both membrane-tethered and cytoplasmic processes.

scholarly journals Author response: HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF-κB/IRF3 nuclear transport

2020 ◽  
Author(s):  
Hataf Khan ◽  
Rebecca P Sumner ◽  
Jane Rasaiyaah ◽  
Choon Ping Tan ◽  
Maria Teresa Rodriguez-Plata ◽  
...  
Keyword(s):  
Immune Activation ◽  
Nuclear Transport ◽  
Innate Immune ◽  
Author Response ◽  
Innate Immune Activation ◽  
Hiv 1

scholarly journals N-terminal acetylation of the yeast Derlin Der1 is essential for Hrd1 ubiquitin-ligase activity toward luminal ER substrates

2013 ◽  
Vol 24 (7) ◽  
pp. 890-900 ◽  
Author(s):  
Dimitrios Zattas ◽  
David J. Adle ◽  
Eric M. Rubenstein ◽  
Mark Hochstrasser
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Fusion Protein ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Recent Analysis ◽  
Specific Class ◽  
Wild Type ◽  
Ubiquitin Ligase Activity

Two conserved ubiquitin ligases, Hrd1 and Doa10, mediate most endoplasmic reticulum–associated protein degradation (ERAD) in yeast. Degradation signals (degrons) recognized by these ubiquitin ligases remain poorly characterized. Doa10 recognizes the Deg1 degron from the MATα2 transcription factor. We previously found that deletion of the gene (NAT3) encoding the catalytic subunit of the NatB N-terminal acetyltransferase weakly stabilized a Deg1-fusion protein. By contrast, a recent analysis of several MATα2 derivatives suggested that N-terminal acetylation of these proteins by NatB was crucial for recognition by Doa10. We now analyze endogenous MATα2 degradation in cells lacking NatB and observe minimal perturbation relative to wild-type cells. However, NatB mutation strongly impairs degradation of ER-luminal Hrd1 substrates. This unexpected defect derives from a failure of Der1, a Hrd1 complex subunit, to be N-terminally acetylated in NatB mutant yeast. We retargeted Der1 to another acetyltransferase to show that it is the only ERAD factor requiring N-terminal acetylation. Preventing Der1 acetylation stimulates its proteolysis via the Hrd1 pathway, at least partially accounting for the ERAD defect observed in the absence of NatB. These results reveal an important role for N-terminal acetylation in controlling Hrd1 ligase activity toward a specific class of ERAD substrates.

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