Imperial College London
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Avinash R. Shenoy

Faculty of Medicine, Department of Infectious Disease

Reader in Innate Immunity and Infection
 
 
 
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Contact

 

+44 (0)20 7594 3785a.shenoy Website

 
 
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Location

 

4.40AFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Eldridge:2017:10.1016/j.celrep.2017.01.015,
author = {Eldridge, MJG and Sanchez, Garrido J and Hoben, GF and Goddard, PJ and Shenoy, AR},
doi = {10.1016/j.celrep.2017.01.015},
journal = {Cell Reports},
pages = {1285--1297},
title = {The atypical ubiquitin E2 conjugase UBE2L3 is an indirect caspase-1 target and controls IL-1beta secretion by inflammasomes},
url = {http://dx.doi.org/10.1016/j.celrep.2017.01.015},
volume = {18},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Caspase-1 activation by inflammasome signalling scaffoldsinitiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-IL-1α into its mature form and directs its secretion, triggers pyroptosis and the release of non-substrate alarmins such as IL-1α and HMGB1. While somecaspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here we report using unbiased proteomics that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1. Caspase-1, but not caspase-4, controlled pyroptosis-and ubiquitin-independent proteasomal degradation of UBE2L3 upon canonical and non-canonical inflammasome activation by sterile danger signals and bacterial infection. Mechanistically, UBE2L3 acted post-translationally to promote K48-ubiquitylation and turnover of pro-IL-1β and dampen mature-IL-1β production. UBE2L3 depletion increased pro-IL-1β levels and mature-IL-1βsecretion by inflammasomes. These findings on UBE2L3 as a molecular rheostat have implications for IL-1-driven pathology in hereditary fever syndromes, and autoinflammatory conditions associated with UBE2L3 polymorphisms.
AU  - Eldridge,MJG
AU  - Sanchez,Garrido J
AU  - Hoben,GF
AU  - Goddard,PJ
AU  - Shenoy,AR
DO  - 10.1016/j.celrep.2017.01.015
EP  - 1297
PY  - 2017///
SN  - 2211-1247
SP  - 1285
TI  - The atypical ubiquitin E2 conjugase UBE2L3 is an indirect caspase-1 target and controls IL-1beta secretion by inflammasomes
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2017.01.015
UR  - http://hdl.handle.net/10044/1/43347
VL  - 18
ER  -
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