BIOSS
Centre for Biological Signalling Studies

The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells

01.07.2015

Dufner A, Kisser A, Niendorf S, Basters A, Reissig S, Schoenle A, Aichem A, Kurz T, Schlosser A, Yablonski D, Groettrup M, Buch T, Waisman A, Schamel WW, Prinz M, Knobeloch KP.

Nat Immunol. 2015;16(9):950-60.

Nat Immunol.            online article

Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3. Caspasedependent processing of USP8 occurred after stimulation of the TCR. T cell- specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Ra mediated by the transcription factor Foxo1. Collectively, our data reveal an unexpected role for USP8 as an immunomodulatory DUB in T cells.