Skip to Main content Skip to Navigation
Journal articles

Loss of the HPV-Infection Resistance EVER2 Protein Impairs NF-κB Signaling Pathways in Keratinocytes

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [40 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-02074029
Contributor : Marie-Luce Kop <>
Submitted on : Wednesday, March 27, 2019 - 2:12:39 PM
Last modification on : Friday, June 12, 2020 - 9:54:02 PM
Long-term archiving on: : Friday, June 28, 2019 - 12:26:12 PM

File

PMID 24586810.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Françoise Vuillier, Guillaume Gaud, Delphine Guillemot, Pierre-Henri Commère, Christian Pons, et al.. Loss of the HPV-Infection Resistance EVER2 Protein Impairs NF-κB Signaling Pathways in Keratinocytes. PLoS ONE, Public Library of Science, 2014, 9 (2), pp.e89479. ⟨10.1371/journal.pone.0089479⟩. ⟨pasteur-02074029⟩

Share

Metrics

Record views

106

Files downloads

264