Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.

Homozygous mutations in EVER genes cause epidermodysplasia verruciformis (EV), characterized by an immune defect and the development of skin cancers associated with β-human papillomavirus (HPV) infections. The effects of EVER protein loss on the keratinocyte immune response remain unknown. We show h...

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Autores principales:	Françoise Vuillier, Guillaume Gaud, Delphine Guillemot, Pierre-Henri Commere, Christian Pons, Michel Favre
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e7a557c92fc4eff9e557c86b7f89b1c
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spelling	oai:doaj.org-article:0e7a557c92fc4eff9e557c86b7f89b1c2021-11-18T08:31:54ZLoss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.1932-620310.1371/journal.pone.0089479https://doaj.org/article/0e7a557c92fc4eff9e557c86b7f89b1c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586810/?tool=EBIhttps://doaj.org/toc/1932-6203Homozygous mutations in EVER genes cause epidermodysplasia verruciformis (EV), characterized by an immune defect and the development of skin cancers associated with β-human papillomavirus (HPV) infections. The effects of EVER protein loss on the keratinocyte immune response remain unknown. We show here that EVER2 plays a critical role in the interplay between the NF-κB and JNK/AP-1 signaling pathways. EVER2-deficient cells overproduce IL-6 following the upregulation of JNK activation. They respond poorly to phorbol ester and TNF via the NF-κB pathway. They have lower levels of IKKα subunit, potentially accounting for impairments of p100 processing and the alternative NF-κB pathway. The loss of EVER2 is associated with an unusual TRAF protein profile. We demonstrate that EVER2 deficiency sustains TRAF2 ubiquitination and decreases the pool of TRAF2 available in the detergent-soluble fraction of the cell. Finally, we demonstrate that EVER2 loss induces constitutive PKCα-dependent c-jun phosphorylation and facilitates activation of the HPV5 long control region through a JNK-dependent pathway. These findings indicate that defects of the EVER2 gene may create an environment conducive to HPV replication and the persistence of lesions with the potential to develop into skin cancer.Françoise VuillierGuillaume GaudDelphine GuillemotPierre-Henri CommereChristian PonsMichel FavrePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89479 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Françoise Vuillier Guillaume Gaud Delphine Guillemot Pierre-Henri Commere Christian Pons Michel Favre Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
description	Homozygous mutations in EVER genes cause epidermodysplasia verruciformis (EV), characterized by an immune defect and the development of skin cancers associated with β-human papillomavirus (HPV) infections. The effects of EVER protein loss on the keratinocyte immune response remain unknown. We show here that EVER2 plays a critical role in the interplay between the NF-κB and JNK/AP-1 signaling pathways. EVER2-deficient cells overproduce IL-6 following the upregulation of JNK activation. They respond poorly to phorbol ester and TNF via the NF-κB pathway. They have lower levels of IKKα subunit, potentially accounting for impairments of p100 processing and the alternative NF-κB pathway. The loss of EVER2 is associated with an unusual TRAF protein profile. We demonstrate that EVER2 deficiency sustains TRAF2 ubiquitination and decreases the pool of TRAF2 available in the detergent-soluble fraction of the cell. Finally, we demonstrate that EVER2 loss induces constitutive PKCα-dependent c-jun phosphorylation and facilitates activation of the HPV5 long control region through a JNK-dependent pathway. These findings indicate that defects of the EVER2 gene may create an environment conducive to HPV replication and the persistence of lesions with the potential to develop into skin cancer.
format	article
author	Françoise Vuillier Guillaume Gaud Delphine Guillemot Pierre-Henri Commere Christian Pons Michel Favre
author_facet	Françoise Vuillier Guillaume Gaud Delphine Guillemot Pierre-Henri Commere Christian Pons Michel Favre
author_sort	Françoise Vuillier
title	Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
title_short	Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
title_full	Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
title_fullStr	Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
title_full_unstemmed	Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.
title_sort	loss of the hpv-infection resistance ever2 protein impairs nf-κb signaling pathways in keratinocytes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0e7a557c92fc4eff9e557c86b7f89b1c
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Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.

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