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Keratinocyte-specific ablation of the NF-κB regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis

Saskia Lippens UGent, S Lefebvre, Barbara Gilbert UGent, Mozes Sze UGent, Michael Devos UGent, Kelly Verhelst UGent, Lars Vereecke UGent, Conor Mc Guire UGent, Chris Guerin UGent and Peter Vandenabeele UGent, et al. (2011) CELL DEATH AND DIFFERENTIATION. 18(12). p.1845-1853
abstract
The ubiquitin-editing enzyme A20 (tumor necrosis factor-alpha-induced protein 3) serves as a critical brake on nuclear factor kappa B (NF-kappa B) signaling. In humans, polymorphisms in or near the A20 gene are associated with several inflammatory disorders, including psoriasis. We show here that epidermis-specific A20-knockout mice (A20(EKO)) develop keratinocyte hyperproliferation, but no signs of skin inflammation, such as immune cell infiltration. However, A20(EKO) mice clearly developed ectodermal organ abnormalities, including disheveled hair, longer nails and sebocyte hyperplasia. This phenotype resembles that of mice overexpressing ectodysplasin-A1 (EDA-A1) or the ectodysplasin receptor (EDAR), suggesting that A20 negatively controls EDAR signaling. We found that A20 inhibited EDAR-induced NF-kappa B signaling independent from its de-ubiquitinating activity. In addition, A20 expression was induced by EDA-A1 in embryonic skin explants, in which its expression was confined to the hair placodes, known to be the site of EDAR expression. In summary, our data indicate that EDAR-induced NF-kappa B levels are controlled by A20, which functions as a negative feedback regulator, to assure proper skin homeostasis and epidermal appendage development.
Please use this url to cite or link to this publication:
author
organization
alternative title
Keratinocyte-specific ablation of the NF-kappa B regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis
year
type
journalArticle (original)
publication status
published
subject
keyword
knockout, NF-kappa B, A20, skin, EDA, HYPOHIDROTIC ECTODERMAL DYSPLASIA, SKIN APPENDAGE DEVELOPMENT, HAIR FOLLICLE DEVELOPMENT, ECTODYSPLASIN-A RECEPTOR, CELL-DEATH, MICE, EDAR, DEFICIENCY, MOUSE, EXPRESSION
journal title
CELL DEATH AND DIFFERENTIATION
Cell Death Differ.
volume
18
issue
12
pages
1845 - 1853
Web of Science type
Article
Web of Science id
000296968000004
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
8.849 (2011)
JCR rank
23/286 (2011)
JCR quartile
1 (2011)
ISSN
1350-9047
DOI
10.1038/cdd.2011.55
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1960388
handle
http://hdl.handle.net/1854/LU-1960388
date created
2011-12-05 17:55:04
date last changed
2013-02-27 09:09:25
@article{1960388,
  abstract     = {The ubiquitin-editing enzyme A20 (tumor necrosis factor-alpha-induced protein 3) serves as a critical brake on nuclear factor kappa B (NF-kappa B) signaling. In humans, polymorphisms in or near the A20 gene are associated with several inflammatory disorders, including psoriasis. We show here that epidermis-specific A20-knockout mice (A20(EKO)) develop keratinocyte hyperproliferation, but no signs of skin inflammation, such as immune cell infiltration. However, A20(EKO) mice clearly developed ectodermal organ abnormalities, including disheveled hair, longer nails and sebocyte hyperplasia. This phenotype resembles that of mice overexpressing ectodysplasin-A1 (EDA-A1) or the ectodysplasin receptor (EDAR), suggesting that A20 negatively controls EDAR signaling. We found that A20 inhibited EDAR-induced NF-kappa B signaling independent from its de-ubiquitinating activity. In addition, A20 expression was induced by EDA-A1 in embryonic skin explants, in which its expression was confined to the hair placodes, known to be the site of EDAR expression. In summary, our data indicate that EDAR-induced NF-kappa B levels are controlled by A20, which functions as a negative feedback regulator, to assure proper skin homeostasis and epidermal appendage development.},
  author       = {Lippens, Saskia and Lefebvre, S and Gilbert, Barbara and Sze, Mozes and Devos, Michael and Verhelst, Kelly and Vereecke, Lars and Mc Guire, Conor and Guerin, Chris and Vandenabeele, Peter and Pasparakis, M and Mikkola, ML and Beyaert, Rudi and Declercq, Wim and van Loo, Geert},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keyword      = {knockout,NF-kappa B,A20,skin,EDA,HYPOHIDROTIC ECTODERMAL DYSPLASIA,SKIN APPENDAGE DEVELOPMENT,HAIR FOLLICLE DEVELOPMENT,ECTODYSPLASIN-A RECEPTOR,CELL-DEATH,MICE,EDAR,DEFICIENCY,MOUSE,EXPRESSION},
  language     = {eng},
  number       = {12},
  pages        = {1845--1853},
  title        = {Keratinocyte-specific ablation of the NF-\ensuremath{\kappa}B regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis},
  url          = {http://dx.doi.org/10.1038/cdd.2011.55},
  volume       = {18},
  year         = {2011},
}

Chicago
Lippens, Saskia, S Lefebvre, Barbara Gilbert, Mozes Sze, Michael Devos, Kelly Verhelst, Lars Vereecke, et al. 2011. “Keratinocyte-specific Ablation of the NF-κB Regulatory Protein A20 (TNFAIP3) Reveals a Role in the Control of Epidermal Homeostasis.” Cell Death and Differentiation 18 (12): 1845–1853.
APA
Lippens, Saskia, Lefebvre, S., Gilbert, B., Sze, M., Devos, M., Verhelst, K., Vereecke, L., et al. (2011). Keratinocyte-specific ablation of the NF-κB regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis. CELL DEATH AND DIFFERENTIATION, 18(12), 1845–1853.
Vancouver
1.
Lippens S, Lefebvre S, Gilbert B, Sze M, Devos M, Verhelst K, et al. Keratinocyte-specific ablation of the NF-κB regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis. CELL DEATH AND DIFFERENTIATION. 2011;18(12):1845–53.
MLA
Lippens, Saskia, S Lefebvre, Barbara Gilbert, et al. “Keratinocyte-specific Ablation of the NF-κB Regulatory Protein A20 (TNFAIP3) Reveals a Role in the Control of Epidermal Homeostasis.” CELL DEATH AND DIFFERENTIATION 18.12 (2011): 1845–1853. Print.