Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells

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+/+ and Nedd4-/- fetal liver chimeras. Nedd4-/- T cells developed normally but proliferated less, produced less interleukin 2 and provided inadequate help to B cells. Nedd4-/- 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
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 > Institute of Infection Immunity and Inflammation
Journal Name:Nature Immunology
ISSN:1529-2908
ISSN (Online):1529-2916
Published Online:19 October 2008

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