@article{86d220405dfb4e3284df74ef63ded97c,
title = "The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules",
abstract = "Salmonella inhibits the adaptive immune response by reducing cell surface levels of mature MHC class II. Alix et al. reveal that the Salmonella effector SteD co-opts TMEM127, a tumor suppressor protein of previously unknown function. TMEM127 binds the E3 ubiquitin ligase WWP2 enabling ubiquitination and degradation of MHCII and SteD.",
keywords = "CRISPR screen, MHCII, Salmonella, SteD, TMEM127, WWP2, dendritic cells, lysosomal degradation, ubiquitination",
author = "Eric Alix and Camilla Godlee and Ondrej Cerny and Samkeliso Blundell and Romina Tocci and Sophie Matthews and Mei Liu and Pruneda, {Jonathan N.} and Swatek, {Kirby N.} and David Komander and Tabitha Sleap and Holden, {David W.}",
note = "Funding Information: We thank members of the Holden laboratory and Teresa Thurston for helpful suggestions. We are grateful to Jacques Neefjes (Leiden University) for providing Mel Juso cells. MutuDCs were a gift from Hans Acha-Orbea (University of Lausanne), and March1 −/− MutuDCs were kindly provided by Justine Mintern (University of Melbourne). The Human GeCKOv2 CRISPR knockout pooled library was a gift from Feng Zhang (Addgene #1000000049). Plasmids encoding HA-tagged WWP2 and the catalytic dead point mutant of WWP2 were gifts from Hugh Pelham. We thank Jess Rowley (MRC CMBI High Throughput Single Cell Analysis Facility) and Jane Srivastava (Imperial College Flow Cytometry Facility) for help with FACS and cell sorting. We are grateful to Janusz D{\c e}bski (Laboratory of Mass Spectrometry, Institute of Biochemistry and Biophysics, Polish Academy of Sciences) for mass spectrometry. This work was supported by grants from the Wellcome Trust ( 209411/Z/17/Z ) to D.W.H. and a Marie Curie Fellowship ( 747392 ) awarded to O.C. Work in the DK laboratory was supported by the Medical Research Council (U105192732), the European Research Council (724804), and the Lister Institute for Preventive Medicine. Funding Information: We thank members of the Holden laboratory and Teresa Thurston for helpful suggestions. We are grateful to Jacques Neefjes (Leiden University) for providing Mel Juso cells. MutuDCs were a gift from Hans Acha-Orbea (University of Lausanne), and March1−/− MutuDCs were kindly provided by Justine Mintern (University of Melbourne). The Human GeCKOv2 CRISPR knockout pooled library was a gift from Feng Zhang (Addgene #1000000049). Plasmids encoding HA-tagged WWP2 and the catalytic dead point mutant of WWP2 were gifts from Hugh Pelham. We thank Jess Rowley (MRC CMBI High Throughput Single Cell Analysis Facility) and Jane Srivastava (Imperial College Flow Cytometry Facility) for help with FACS and cell sorting. We are grateful to Janusz D{\c e}bski (Laboratory of Mass Spectrometry, Institute of Biochemistry and Biophysics, Polish Academy of Sciences) for mass spectrometry. This work was supported by grants from the Wellcome Trust (209411/Z/17/Z) to D.W.H. and a Marie Curie Fellowship (747392) awarded to O.C. Work in the DK laboratory was supported by the Medical Research Council (U105192732), the European Research Council (724804), and the Lister Institute for Preventive Medicine. Conceptualization, D.W.H. E.A. O.C. C.G. D.K. and J.N.P.; Investigation, E.A. O.C. C.G. S.B. R.T. S.M. M.L. J.N.P. K.N.S. and T.S.; Writing – Original Draft, D.W.H. E.A. O.C. and C.G.; Supervision, E.A. O.C. C.G. and D.W.H.; Funding Acquisition, D.W.H. and O.C. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Imperial College London",
year = "2020",
month = jul,
day = "8",
doi = "10.1016/j.chom.2020.04.024",
language = "English (US)",
volume = "28",
pages = "54--68.e7",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",
}