rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
6
|
pubmed:dateCreated |
2006-12-18
|
pubmed:abstractText |
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.
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pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
1074-7613
|
pubmed:author |
pubmed-author:BrionesNatalieN,
pubmed-author:CaoXiaoX,
pubmed-author:KapplerJohnJ,
pubmed-author:KirbyPatriciaP,
pubmed-author:MacLeodMeganM,
pubmed-author:MarrackPhilippaP,
pubmed-author:OliverPaula MPM,
pubmed-author:ShiPeijunP,
pubmed-author:WhiteJaniceJ,
pubmed-author:WorthenGeorge ScottGS,
pubmed-author:YangBaoliB
|
pubmed:issnType |
Print
|
pubmed:volume |
25
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
929-40
|
pubmed:dateRevised |
2010-12-3
|
pubmed:meshHeading |
pubmed-meshheading:17137798-Animals,
pubmed-meshheading:17137798-Blotting, Western,
pubmed-meshheading:17137798-Carrier Proteins,
pubmed-meshheading:17137798-Cytokines,
pubmed-meshheading:17137798-Flow Cytometry,
pubmed-meshheading:17137798-Inflammation,
pubmed-meshheading:17137798-Lymphocyte Activation,
pubmed-meshheading:17137798-Membrane Proteins,
pubmed-meshheading:17137798-Mice,
pubmed-meshheading:17137798-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:17137798-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17137798-T-Lymphocytes,
pubmed-meshheading:17137798-Th2 Cells,
pubmed-meshheading:17137798-Ubiquitin-Protein Ligases
|
pubmed:year |
2006
|
pubmed:articleTitle |
Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation.
|
pubmed:affiliation |
Howard Hughes Medical Institute, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colorado 80206, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|