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Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD

Hovelmeyer, Nadine ; Wunderlich, F Thomas ; Massoumi, Ramin LU ; Jakobsen, Charlotte G ; Song, Jian ; Worns, Marcus A ; Merkwirth, Carsten ; Kovalenko, Andrew ; Aumailley, Monique and Strand, Dennis , et al. (2007) In Journal of Experimental Medicine 204(11). p.2615-2627
Abstract
B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-kappaB (NF-kappaB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLD(ex7/8) mice), which is a deubiquitinating enzyme that is integral to NF-kappaB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves... (More)
B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-kappaB (NF-kappaB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLD(ex7/8) mice), which is a deubiquitinating enzyme that is integral to NF-kappaB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves exhibit prolonged survival and manifest a variety of signaling disarrangements that do not occur in mice with a complete deletion of CYLD. Although both the full-length and the mutant CYLD are able to interact with Bcl-3, a predominant nuclear accumulation of Bcl-3 occurs in the CYLD mutant B cells. More dramatic, however, is the accumulation of the NF-kappaB proteins p100 and RelB in CYLD(ex7/8) B cells, which, presumably in combination with nuclear Bcl-3, results in increased levels of Bcl-2 expression. These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
204
issue
11
pages
2615 - 2627
publisher
Rockefeller University Press
external identifiers
  • pmid:17923499
  • scopus:35748956767
  • pmid:17923499
ISSN
1540-9538
DOI
10.1084/jem.20070318
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Cell Pathology (013031400), Pathology, (Lund) (013030000)
id
e119e845-c4d5-43e0-b0f2-f3409d0ece96 (old id 1141263)
date added to LUP
2016-04-04 09:15:32
date last changed
2022-05-01 08:43:39
@article{e119e845-c4d5-43e0-b0f2-f3409d0ece96,
  abstract     = {{B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-kappaB (NF-kappaB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLD(ex7/8) mice), which is a deubiquitinating enzyme that is integral to NF-kappaB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves exhibit prolonged survival and manifest a variety of signaling disarrangements that do not occur in mice with a complete deletion of CYLD. Although both the full-length and the mutant CYLD are able to interact with Bcl-3, a predominant nuclear accumulation of Bcl-3 occurs in the CYLD mutant B cells. More dramatic, however, is the accumulation of the NF-kappaB proteins p100 and RelB in CYLD(ex7/8) B cells, which, presumably in combination with nuclear Bcl-3, results in increased levels of Bcl-2 expression. These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants.}},
  author       = {{Hovelmeyer, Nadine and Wunderlich, F Thomas and Massoumi, Ramin and Jakobsen, Charlotte G and Song, Jian and Worns, Marcus A and Merkwirth, Carsten and Kovalenko, Andrew and Aumailley, Monique and Strand, Dennis and Bruning, Jens C and Galle, Peter R and Wallach, David and Fässler, Reinhard}},
  issn         = {{1540-9538}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2615--2627}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Experimental Medicine}},
  title        = {{Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD}},
  url          = {{http://dx.doi.org/10.1084/jem.20070318}},
  doi          = {{10.1084/jem.20070318}},
  volume       = {{204}},
  year         = {{2007}},
}