Yang, B., Gay, D. L., Macleod, M. K.L. , Cao, X., Hala, T., Sweezer, E. M., Kappler, J., Marrack, P. and Oliver, P. M. (2008) Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells. Nature Immunology, 9(12), pp. 1356-1363. (doi: 10.1038/ni.1670) (PMID:18931680) (PMCID:PMC2935464)
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Abstract
Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targetsin vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization. To test whether loss of Nedd4 affects T cells in the same way, we generatedNedd4<sup>+/+</sup> and Nedd4<sup>-/-</sup> fetal liver chimeras. Nedd4<sup>-/-</sup> T cells developed normally but proliferated less, produced less interleukin 2 and provided inadequate help to B cells. Nedd4<sup>-/-</sup> T cells contained more of the E3 ubiquitin ligase Cbl-b, and Nedd4 was required for polyubiquitination of Cbl-b induced by CD28 costimulation. Our data demonstrate that Nedd4 promotes the conversion of naive T cells into activated T cells. We propose that Nedd4 and Itch ubiquitinate distinct target proteins in vivo.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Macleod, Dr Megan |
Authors: | Yang, B., Gay, D. L., Macleod, M. K.L., Cao, X., Hala, T., Sweezer, E. M., Kappler, J., Marrack, P., and Oliver, P. M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Nature Immunology |
ISSN: | 1529-2908 |
ISSN (Online): | 1529-2916 |
Published Online: | 19 October 2008 |
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