Imperial College London
Alternate

ProfessorDavidHolden

Faculty of Medicine, Department of Infectious Disease

Professor
 
 
 
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Contact

 

+44 (0)20 7594 3073d.holden

 
 
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Location

 

221Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Alix:2020:10.1016/j.chom.2020.04.024,
author = {Alix, E and Godlee, C and Cerny, O and Blundell, S and Tocci, R and Liu, M and Pruneda, JN and Swatek, KN and Komander, D and Sleap, T and Holden, D},
doi = {10.1016/j.chom.2020.04.024},
journal = {Cell Host and Microbe},
pages = {54--68.e7},
title = {The tumor suppressor TMEM127 is a Nedd4-family E3 ligase adaptor required by Salmonella SteD to ubiquitinate and degrade MHC class II molecules},
url = {http://dx.doi.org/10.1016/j.chom.2020.04.024},
volume = {28},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The Salmonella enterica effector SteD depletes mature MHC class II (mMHCII) molecules from the surface of infected antigen-presenting cells through ubiquitination of the cytoplasmic tail of the mMHCII β chain. Here, through a genome-wide mutant screen of human antigen-presenting cells, we show that the NEDD4 family HECT E3 ubiquitin ligase WWP2 and a tumor-suppressing transmembrane protein of unknown biochemical function, TMEM127, are required for SteD-dependent ubiquitination of mMHCII. Although evidently not involved in normal regulation of mMHCII, TMEM127 was essential for SteD to suppress both mMHCII antigen presentation in mouse dendritic cells and MHCII-dependent CD4+ T cell activation. We found that TMEM127 contains a canonical PPxY motif, which was required for binding to WWP2. SteD bound to TMEM127 and enabled TMEM127 to interact with and induce ubiquitination of mature MHCII. Furthermore, SteD also underwent TMEM127- and WWP2-dependent ubiquitination, which both contributed to its degradation and augmented its activity on mMHCII.
AU  - Alix,E
AU  - Godlee,C
AU  - Cerny,O
AU  - Blundell,S
AU  - Tocci,R
AU  - Liu,M
AU  - Pruneda,JN
AU  - Swatek,KN
AU  - Komander,D
AU  - Sleap,T
AU  - Holden,D
DO  - 10.1016/j.chom.2020.04.024
EP  - 68
PY  - 2020///
SN  - 1931-3128
SP  - 54
TI  - The tumor suppressor TMEM127 is a Nedd4-family E3 ligase adaptor required by Salmonella SteD to ubiquitinate and degrade MHC class II molecules
T2  - Cell Host and Microbe
UR  - http://dx.doi.org/10.1016/j.chom.2020.04.024
UR  - https://www.sciencedirect.com/science/article/pii/S1931312820302511?via%3Dihub
UR  - http://hdl.handle.net/10044/1/79916
VL  - 28
ER  -
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