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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) , Peter Vandenabeele (UGent) , et al.
(2011) CELL DEATH AND DIFFERENTIATION. 18(12). p.1845-1853
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
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

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Citation

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MLA
Lippens, Saskia, 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, vol. 18, no. 12, 2011, pp. 1845–53.
APA
Lippens, S., Lefebvre, S., Gilbert, B., Sze, M., Devos, M., Verhelst, K., … van Loo, G. (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.
Chicago author-date
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): 1845–53.
Chicago author-date (all authors)
Lippens, Saskia, S Lefebvre, Barbara Gilbert, Mozes Sze, Michael Devos, Kelly Verhelst, Lars Vereecke, Conor Mc Guire, Chris Guerin, Peter Vandenabeele, M Pasparakis, ML Mikkola, Rudi Beyaert, Wim Declercq, and Geert van Loo. 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.
IEEE
[1]
S. Lippens 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, vol. 18, no. 12, pp. 1845–1853, 2011.
@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},
  keywords     = {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-κB 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},
}

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