Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation

Oliver, P. M. et al. (2006) Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Immunity, 25(6), pp. 929-940. (doi: 10.1016/j.immuni.2006.10.012) (PMID:17137798) (PMCID:PMC2955961)

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Abstract

Nedd4 family interacting protein-1 (Ndfip1) is a protein whose only known function is that it binds Nedd4, a HECT-type E3 ubiquitin ligase. Here we show that mice lacking Ndfip1 developed severe inflammation of the skin and lung and died prematurely. This condition was due to a defect in Ndfip1−/− T cells. Ndfip1−/− T cells were activated, and they proliferated and adopted a T helper 2 (Th2) phenotype more readily than did their Ndfip1+/+ counterparts. This phenotype resembled that of Itchy mutant mice, suggesting that Ndfip1 might affect the function of Itch, an E3 ubiquitin ligase. We show that T cell activation promoted both Ndfip1 expression and its association with Itch. In the absence of Ndfip1, JunB half-life was prolonged after T cell activation. Thus, in the absence of Ndfip1, Itch is inactive and JunB accumulates. As a result, T cells produce Th2 cytokines and promote Th2-mediated inflammatory disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macleod, Dr Megan
Authors: Oliver, P. M., Cao, X., Worthen, G. S., Shi, P., Briones, N., Macleod, M., White, J., Kirby, P., Kappler, J., Marrack, P., and Yang, B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Elsevier B.V.
ISSN:1074-7613
ISSN (Online):1097-4180
Published Online:30 November 2006

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