Brady, Kevin J. and Fitzgerald, Stephen and Moynagh, Paul N.
(2000)
Tumour-necrosis-factor-receptor-associated factor 6, NF-jB-inducing kinase
and IjB kinases mediate IgE isotype switching in response to CD40.
Biochemical Journal, 350.
pp. 735-740.
ISSN 0264-6021
Abstract
The process of IgE switching requires the prior transcription of
the unrearranged Ce gene, which leads to its recombination
with the VDJ region. The activation of NF-jB by CD40 is a key
process in facilitating this transcription by promoting the activation
of the Ce promoter. The present study explores the
uncharacterized signalling pathways employed by CD40 in
activating NF-jB by the overexpression of genes encoding wildtype
and dominant-negative forms of the signalling components
tumour-necrosis-factor-receptor-associated factor 6 (TRAF-6),
NF-jB-inducing kinase (NIK), IjB kinase (IKK)-1 and IKK-2
in the BJAB B-cell line. The overexpression of TRAF-6 or NIK
was sufficient to activate NF-jB and the Ce promoter, whereas
their dominant-negative counterparts decreased the ability of CD40 to activate NF-jB and the Ce promoter. The overexpression
of wild-type IKK-1 or IKK-2 seemed to cause toxic
effects on the cells, whereas the dominant-negative forms were
selective in their blockade of NF-jB and the Ce promoter. These
results suggest that CD40 employs TRAF-6, which presumably
recruits NIK, which in turn employs IKK-1}IKK-2 to activate
NF-jB and the Ce promoter, the prologue to IgE switching.
Thus the findings define a crucially important pathway in the
generation of allergic states.
| Item Type: |
Article
|
| Keywords: |
Tumour-necrosis-factor-receptor-associated factor 6; NF-jB-inducing kinase; IjB kinases; IgE isotype switching; CD40; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
7221 |
| Depositing User: |
Professor Paul Moynagh
|
| Date Deposited: |
09 Aug 2016 14:29 |
| Journal or Publication Title: |
Biochemical Journal |
| Publisher: |
Portland Press |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
Repository Staff Only(login required)
 |
Item control page |
Downloads per month over past year
Origin of downloads
Altmetric
Altmetric