Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.

<h4>Background</h4>TEA domain (TEAD) proteins are highly conserved transcription factors involved in embryonic development and differentiation of various tissues. More recently, emerging evidences for a contribution of these proteins towards apoptosis and cell proliferation regulation ha...

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Autores principales:	André Landin Malt, Julie Cagliero, Kevin Legent, Joël Silber, Alain Zider, Domenico Flagiello
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c26a4fd6f684ee28f4c970f657889ad
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spelling	oai:doaj.org-article:9c26a4fd6f684ee28f4c970f657889ad2021-11-18T07:04:22ZAlteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.1932-620310.1371/journal.pone.0045498https://doaj.org/article/9c26a4fd6f684ee28f4c970f657889ad2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029054/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>TEA domain (TEAD) proteins are highly conserved transcription factors involved in embryonic development and differentiation of various tissues. More recently, emerging evidences for a contribution of these proteins towards apoptosis and cell proliferation regulation have also been proposed. These effects appear to be mediated by the interaction between TEAD and its co-activator Yes-Associated Protein (YAP), the downstream effector of the Hippo tumour suppressor pathway.<h4>Methodology/principal findings</h4>We further investigated the mechanisms underlying TEAD-mediated apoptosis regulation and showed that overexpression or RNAi-mediated silencing of the TEAD1 protein is sufficient to protect mammalian cell lines from induced apoptosis, suggesting a proapoptotic function for TEAD1 and a non physiological cytoprotective effect for overexpressed TEAD1. Moreover we show that the apoptotic resistance conferred by altered TEAD1 expression is mediated by the transcriptional up-regulation of Livin, a member of the Inhibitor of Apoptosis Protein (IAP) family. In addition, we show that overexpression of a repressive form of TEAD1 can induce Livin up-regulation, indicating that the effect of TEAD1 on Livin expression is indirect and favoring a model in which TEAD1 activates a repressor of Livin by interacting with a limiting cofactor that gets titrated upon TEAD1 up-regulation. Interestingly, we show that overexpression of a mutated form of TEAD1 (Y421H) implicated in Sveinsson's chorioretinal atrophy that strongly reduces its interaction with YAP as well as its activation, can induce Livin expression and protect cells from induced apoptosis, suggesting that YAP is not the cofactor involved in this process.<h4>Conclusions/significance</h4>Taken together our data reveal a new, Livin-dependent, apoptotic role for TEAD1 in mammals and provide mechanistic insight downstream of TEAD1 deregulation in cancers.André Landin MaltJulie CaglieroKevin LegentJoël SilberAlain ZiderDomenico FlagielloPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45498 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q André Landin Malt Julie Cagliero Kevin Legent Joël Silber Alain Zider Domenico Flagiello Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
description	<h4>Background</h4>TEA domain (TEAD) proteins are highly conserved transcription factors involved in embryonic development and differentiation of various tissues. More recently, emerging evidences for a contribution of these proteins towards apoptosis and cell proliferation regulation have also been proposed. These effects appear to be mediated by the interaction between TEAD and its co-activator Yes-Associated Protein (YAP), the downstream effector of the Hippo tumour suppressor pathway.<h4>Methodology/principal findings</h4>We further investigated the mechanisms underlying TEAD-mediated apoptosis regulation and showed that overexpression or RNAi-mediated silencing of the TEAD1 protein is sufficient to protect mammalian cell lines from induced apoptosis, suggesting a proapoptotic function for TEAD1 and a non physiological cytoprotective effect for overexpressed TEAD1. Moreover we show that the apoptotic resistance conferred by altered TEAD1 expression is mediated by the transcriptional up-regulation of Livin, a member of the Inhibitor of Apoptosis Protein (IAP) family. In addition, we show that overexpression of a repressive form of TEAD1 can induce Livin up-regulation, indicating that the effect of TEAD1 on Livin expression is indirect and favoring a model in which TEAD1 activates a repressor of Livin by interacting with a limiting cofactor that gets titrated upon TEAD1 up-regulation. Interestingly, we show that overexpression of a mutated form of TEAD1 (Y421H) implicated in Sveinsson's chorioretinal atrophy that strongly reduces its interaction with YAP as well as its activation, can induce Livin expression and protect cells from induced apoptosis, suggesting that YAP is not the cofactor involved in this process.<h4>Conclusions/significance</h4>Taken together our data reveal a new, Livin-dependent, apoptotic role for TEAD1 in mammals and provide mechanistic insight downstream of TEAD1 deregulation in cancers.
format	article
author	André Landin Malt Julie Cagliero Kevin Legent Joël Silber Alain Zider Domenico Flagiello
author_facet	André Landin Malt Julie Cagliero Kevin Legent Joël Silber Alain Zider Domenico Flagiello
author_sort	André Landin Malt
title	Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
title_short	Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
title_full	Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
title_fullStr	Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
title_full_unstemmed	Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.
title_sort	alteration of tead1 expression levels confers apoptotic resistance through the transcriptional up-regulation of livin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9c26a4fd6f684ee28f4c970f657889ad
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Alteration of TEAD1 expression levels confers apoptotic resistance through the transcriptional up-regulation of Livin.

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