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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586810/?tool=EBI |
| _version_ | 1818402226343772160 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T08:05:00Z |
| format | Article |
| id | doaj.art-0e7a557c92fc4eff9e557c86b7f89b1c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:05:00Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0e7a557c92fc4eff9e557c86b7f89b1c2022-12-21T23:10:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8947910.1371/journal.pone.0089479Loss of the HPV-infection resistance EVER2 protein impairs NF-κB signaling pathways in keratinocytes.Françoise VuillierGuillaume GaudDelphine GuillemotPierre-Henri CommereChristian PonsMichel FavreHomozygous 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586810/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586810/?tool=EBI |
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