English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules

Alix, E., Godlee, C., Cerny, O., Blundell, S., Tocci, R., Matthews, S., et al. (2020). The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules. CELL HOST & MICROBE, 28(1), 54-68. doi:10.1016/j.chom.2020.04.024.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0006-C9FF-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-CA00-6
Genre: Journal Article

Files

show Files
hide Files
:
1-s2.0-S1931312820302511-main.pdf (Any fulltext), 6MB
Name:
1-s2.0-S1931312820302511-main.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
open access article
License:
-

Locators

show

Creators

show
hide
 Creators:
Alix, Eric1, Author
Godlee, Camilla1, Author
Cerny, Ondrej1, Author
Blundell, Samkeliso1, Author
Tocci, Romina1, Author
Matthews, Sophie1, Author
Liu, Mei1, Author
Pruneda, Jonathan N.1, Author
Swatek, Kirby N.1, Author
Komander, David2, Author              
Sleap, Tabitha1, Author
Holden, David W.1, Author
Affiliations:
1external, ou_persistent22              
2Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466699              

Content

show
hide
Free keywords: DENDRITIC CELLS; WWP2; POLYUBIQUITINATION; SUSCEPTIBILITY; MUTATIONS
 Abstract: 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 b 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.

Details

show
hide
Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 22
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CELL HOST & MICROBE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 28 (1) Sequence Number: - Start / End Page: 54 - 68 Identifier: ISSN: 1931-3128