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Naturally occurring short splice variant of CYLD positively regulates dendritic cell function

Srokowski, Cathy Cecilia ; Masri, Joumana ; Hoevelmeyer, Nadine ; Krembel, Anna Katharina ; Tertilt, Christine ; Strand, Dennis ; Mahnke, Karsten ; Massoumi, Ramin LU ; Waisman, Ari and Schild, Hansjoerg (2009) In Blood 113(23). p.5891-5895
Abstract
Deubiquitination of NF-kappa B members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow-derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205-mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-kappa B activity accompanied by an increased nuclear translocation of the I kappa B molecule Bcl-3,... (More)
Deubiquitination of NF-kappa B members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow-derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205-mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-kappa B activity accompanied by an increased nuclear translocation of the I kappa B molecule Bcl-3, along with nuclear p50 and p65. This suggests that, in contrast to flCYLD, sCYLD is a positive regulator of NF-kappa B activity, and its overexpression induces a hyperactive phenotype in DCs. (Blood. 2009; 113: 5891-5895) (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
113
issue
23
pages
5891 - 5895
publisher
American Society of Hematology
external identifiers
  • wos:000266656100030
  • scopus:67651091771
  • pmid:19342479
ISSN
1528-0020
DOI
10.1182/blood-2008-08-175489
language
English
LU publication?
yes
id
2e390215-90a5-4feb-8e64-a6a56627fdea (old id 1444126)
date added to LUP
2016-04-01 12:07:10
date last changed
2022-01-26 23:03:03
@article{2e390215-90a5-4feb-8e64-a6a56627fdea,
  abstract     = {{Deubiquitination of NF-kappa B members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow-derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205-mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-kappa B activity accompanied by an increased nuclear translocation of the I kappa B molecule Bcl-3, along with nuclear p50 and p65. This suggests that, in contrast to flCYLD, sCYLD is a positive regulator of NF-kappa B activity, and its overexpression induces a hyperactive phenotype in DCs. (Blood. 2009; 113: 5891-5895)}},
  author       = {{Srokowski, Cathy Cecilia and Masri, Joumana and Hoevelmeyer, Nadine and Krembel, Anna Katharina and Tertilt, Christine and Strand, Dennis and Mahnke, Karsten and Massoumi, Ramin and Waisman, Ari and Schild, Hansjoerg}},
  issn         = {{1528-0020}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{5891--5895}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Naturally occurring short splice variant of CYLD positively regulates dendritic cell function}},
  url          = {{http://dx.doi.org/10.1182/blood-2008-08-175489}},
  doi          = {{10.1182/blood-2008-08-175489}},
  volume       = {{113}},
  year         = {{2009}},
}