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 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.
journal_name
Cell Host Microbejournal_title
Cell host & microbeauthors
Alix E,Godlee C,Cerny O,Blundell S,Tocci R,Matthews S,Liu M,Pruneda JN,Swatek KN,Komander D,Sleap T,Holden DWdoi
10.1016/j.chom.2020.04.024subject
Has Abstractpub_date
2020-07-08 00:00:00pages
54-68.e7issue
1eissn
1931-3128issn
1934-6069pii
S1931-3128(20)30251-1journal_volume
28pub_type
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