Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD
(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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https://lup.lub.lu.se/record/1141263
- author
- organization
- publishing date
- 2007
- 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}}, }