Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells

Sascha Rutz, Nobuhiko Kayagaki, Qui T. Phung, Celine Eidenschenk, Rajkumar Noubade, Xiaoting Wang, Justin Lesch, Rongze Lu, Kim Newton, Oscar W. Huang, Andrea G. Cochran, Mark Vasser, Benjamin P. Fauber, Jason DeVoss, Joshua Webster, Lauri Diehl, Zora Modrusan, Donald S. Kirkpatrick, Jennie R. Lill, Wenjun Ouyang () and Vishva M. Dixit ()
Additional contact information
Sascha Rutz: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Nobuhiko Kayagaki: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Qui T. Phung: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Celine Eidenschenk: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Rajkumar Noubade: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Xiaoting Wang: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Justin Lesch: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Rongze Lu: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Kim Newton: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Oscar W. Huang: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Andrea G. Cochran: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Mark Vasser: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Benjamin P. Fauber: Discovery Chemistry, Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Jason DeVoss: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Joshua Webster: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Lauri Diehl: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Zora Modrusan: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Donald S. Kirkpatrick: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Jennie R. Lill: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Wenjun Ouyang: Genentech, 1 DNA Way, South San Francisco, California 94080, USA
Vishva M. Dixit: Genentech, 1 DNA Way, South San Francisco, California 94080, USA

Nature, 2015, vol. 518, issue 7539, 417-421

Abstract: The deubiquitinase enzyme DUBA is shown to act as a negative regulator of interleukin-17A (IL-17A) in TH17 cells; DUBA interacts with and stabilizes the ubiquitin ligase UBR5, which in turn targets RORγt for degradation in the proteaseome, thus limiting IL-17A production.

Date: 2015
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DOI: 10.1038/nature13979

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