EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.

Human papillomaviruses (HPV) cause a variety of mucosal and skin lesions ranging from benign proliferations to invasive carcinomas. The clinical manifestations of infection are determined by host-related factors that define the natural anti-HPV barrier. Key elements of this barrier are the EVER1 and...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maciej Lazarczyk, Cécile Dalard, Myriam Hayder, Loïc Dupre, Béatrice Pignolet, Slawomir Majewski, Francoise Vuillier, Michel Favre, Roland S Liblau
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5df31c6655074a36b9bcd63af613e63d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5df31c6655074a36b9bcd63af613e63d
record_format	dspace
spelling	oai:doaj.org-article:5df31c6655074a36b9bcd63af613e63d2021-11-18T07:14:05ZEVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.1932-620310.1371/journal.pone.0039995https://doaj.org/article/5df31c6655074a36b9bcd63af613e63d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761942/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Human papillomaviruses (HPV) cause a variety of mucosal and skin lesions ranging from benign proliferations to invasive carcinomas. The clinical manifestations of infection are determined by host-related factors that define the natural anti-HPV barrier. Key elements of this barrier are the EVER1 and EVER2 proteins, as deficiency in either one of the EVER proteins leads to Epidermodysplasia Verruciformis (EV), a genodermatosis associated with HPV-induced skin carcinoma. Although EVERs have been shown to regulate zinc homeostasis in keratinocytes, their expression and function in other cell types that may participate to the anti-HPV barrier remain to be investigated. In this work, we demonstrate that EVER genes are expressed in different tissues, and most notably in lymphocytes. Interestingly, in contrast to the skin, where EVER2 transcripts are hardly detectable, EVER genes are both abundantly expressed in murine and human T cells. Activation of CD4+ and CD8+ T cells via the TCR triggers a rapid and profound decrease in EVER expression, accompanied by an accumulation of free Zn(2+) ions. Thus, EVER proteins may be involved in the regulation of cellular zinc homeostasis in lymphocytes. Consistent with this hypothesis, we show that the concentration of Zn(2+) ions is elevated in lymphoblastoid cells or primary T cells from EVER2-deficient patients. Interestingly, we also show that Zn(2+) excess blocks T-cell activation and proliferation. Therefore, EVER proteins appear as key components of the activation-dependent regulation of Zn(2+) concentration in T cells. However, the impact of EVER-deficiency in T cells on EV pathogenesis remains to be elucidated.Maciej LazarczykCécile DalardMyriam HayderLoïc DupreBéatrice PignoletSlawomir MajewskiFrancoise VuillierMichel FavreRoland S LiblauPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39995 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maciej Lazarczyk Cécile Dalard Myriam Hayder Loïc Dupre Béatrice Pignolet Slawomir Majewski Francoise Vuillier Michel Favre Roland S Liblau EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
description	Human papillomaviruses (HPV) cause a variety of mucosal and skin lesions ranging from benign proliferations to invasive carcinomas. The clinical manifestations of infection are determined by host-related factors that define the natural anti-HPV barrier. Key elements of this barrier are the EVER1 and EVER2 proteins, as deficiency in either one of the EVER proteins leads to Epidermodysplasia Verruciformis (EV), a genodermatosis associated with HPV-induced skin carcinoma. Although EVERs have been shown to regulate zinc homeostasis in keratinocytes, their expression and function in other cell types that may participate to the anti-HPV barrier remain to be investigated. In this work, we demonstrate that EVER genes are expressed in different tissues, and most notably in lymphocytes. Interestingly, in contrast to the skin, where EVER2 transcripts are hardly detectable, EVER genes are both abundantly expressed in murine and human T cells. Activation of CD4+ and CD8+ T cells via the TCR triggers a rapid and profound decrease in EVER expression, accompanied by an accumulation of free Zn(2+) ions. Thus, EVER proteins may be involved in the regulation of cellular zinc homeostasis in lymphocytes. Consistent with this hypothesis, we show that the concentration of Zn(2+) ions is elevated in lymphoblastoid cells or primary T cells from EVER2-deficient patients. Interestingly, we also show that Zn(2+) excess blocks T-cell activation and proliferation. Therefore, EVER proteins appear as key components of the activation-dependent regulation of Zn(2+) concentration in T cells. However, the impact of EVER-deficiency in T cells on EV pathogenesis remains to be elucidated.
format	article
author	Maciej Lazarczyk Cécile Dalard Myriam Hayder Loïc Dupre Béatrice Pignolet Slawomir Majewski Francoise Vuillier Michel Favre Roland S Liblau
author_facet	Maciej Lazarczyk Cécile Dalard Myriam Hayder Loïc Dupre Béatrice Pignolet Slawomir Majewski Francoise Vuillier Michel Favre Roland S Liblau
author_sort	Maciej Lazarczyk
title	EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
title_short	EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
title_full	EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
title_fullStr	EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
title_full_unstemmed	EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.
title_sort	ever proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon t-cell activation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5df31c6655074a36b9bcd63af613e63d
work_keys_str_mv	AT maciejlazarczyk everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT ceciledalard everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT myriamhayder everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT loicdupre everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT beatricepignolet everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT slawomirmajewski everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT francoisevuillier everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT michelfavre everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation AT rolandsliblau everproteinskeyelementsofthenaturalantihumanpapillomavirusbarrierareregulatedupontcellactivation
_version_	1718423727090171904

EVER proteins, key elements of the natural anti-human papillomavirus barrier, are regulated upon T-cell activation.

Ejemplares similares