Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.

<h4>Background</h4>Active infection by bovine papillomavirus type 2 (BPV-2) was documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as papillary and four as invasive urothelial cancers.<...

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Autores principales:	Sante Roperto, Valeria Russo, Giuseppe Borzacchiello, Chiara Urraro, Roberta Lucà, Iolanda Esposito, Marita Georgia Riccardi, Cinzia Raso, Marco Gaspari, Dora Maria Ceccarelli, Rocco Galasso, Franco Roperto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae1628fdd3ee4c9a929fde3176194580
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spelling	oai:doaj.org-article:ae1628fdd3ee4c9a929fde31761945802021-11-18T08:31:24ZBovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.1932-620310.1371/journal.pone.0088860https://doaj.org/article/ae1628fdd3ee4c9a929fde31761945802014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586417/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Active infection by bovine papillomavirus type 2 (BPV-2) was documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as papillary and four as invasive urothelial cancers.<h4>Methods and findings</h4>In all cancer samples, PCR analysis revealed a BPV-2-specific 503 bp DNA fragment. E5 protein, the major oncoprotein of the virus, was shown both by immunoprecipitation and immunohistochemical analysis. E5 was found to bind to the activated (phosphorylated) form of the platelet derived growth factor β receptor. PDGFβR immunoprecipitation from bladder tumor samples and from normal bladder tissue used as control revealed a protein band which was present in the pull-down from bladder cancer samples only. The protein was identified with mass spectrometry as "V₁-ATPase subunit D", a component of the central stalk of the V₁-ATPase vacuolar pump. The subunit D was confirmed in this complex by coimmunoprecipitation investigations and it was found to colocalize with the receptor. The subunit D was also shown to be overexpressed by Western blot, RT-PCR and immunofluorescence analyses. Immunoprecipitation and immunofluorescence also revealed that E5 oncoprotein was bound to the subunit D.<h4>Conclusion</h4>For the first time, a tri-component complex composed of E5/PDGFβR/subunit D has been documented in vivo. Previous in vitro studies have shown that the BPV-2 E5 oncoprotein binds to the proteolipid c ring of the V₀-ATPase sector. We suggest that the E5/PDGFβR/subunit D complex may perturb proteostasis, organelle and cytosol homeostasis, which can result in altered protein degradation and in autophagic responses.Sante RopertoValeria RussoGiuseppe BorzacchielloChiara UrraroRoberta LucàIolanda EspositoMarita Georgia RiccardiCinzia RasoMarco GaspariDora Maria CeccarelliRocco GalassoFranco RopertoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88860 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sante Roperto Valeria Russo Giuseppe Borzacchiello Chiara Urraro Roberta Lucà Iolanda Esposito Marita Georgia Riccardi Cinzia Raso Marco Gaspari Dora Maria Ceccarelli Rocco Galasso Franco Roperto Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
description	<h4>Background</h4>Active infection by bovine papillomavirus type 2 (BPV-2) was documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as papillary and four as invasive urothelial cancers.<h4>Methods and findings</h4>In all cancer samples, PCR analysis revealed a BPV-2-specific 503 bp DNA fragment. E5 protein, the major oncoprotein of the virus, was shown both by immunoprecipitation and immunohistochemical analysis. E5 was found to bind to the activated (phosphorylated) form of the platelet derived growth factor β receptor. PDGFβR immunoprecipitation from bladder tumor samples and from normal bladder tissue used as control revealed a protein band which was present in the pull-down from bladder cancer samples only. The protein was identified with mass spectrometry as "V₁-ATPase subunit D", a component of the central stalk of the V₁-ATPase vacuolar pump. The subunit D was confirmed in this complex by coimmunoprecipitation investigations and it was found to colocalize with the receptor. The subunit D was also shown to be overexpressed by Western blot, RT-PCR and immunofluorescence analyses. Immunoprecipitation and immunofluorescence also revealed that E5 oncoprotein was bound to the subunit D.<h4>Conclusion</h4>For the first time, a tri-component complex composed of E5/PDGFβR/subunit D has been documented in vivo. Previous in vitro studies have shown that the BPV-2 E5 oncoprotein binds to the proteolipid c ring of the V₀-ATPase sector. We suggest that the E5/PDGFβR/subunit D complex may perturb proteostasis, organelle and cytosol homeostasis, which can result in altered protein degradation and in autophagic responses.
format	article
author	Sante Roperto Valeria Russo Giuseppe Borzacchiello Chiara Urraro Roberta Lucà Iolanda Esposito Marita Georgia Riccardi Cinzia Raso Marco Gaspari Dora Maria Ceccarelli Rocco Galasso Franco Roperto
author_facet	Sante Roperto Valeria Russo Giuseppe Borzacchiello Chiara Urraro Roberta Lucà Iolanda Esposito Marita Georgia Riccardi Cinzia Raso Marco Gaspari Dora Maria Ceccarelli Rocco Galasso Franco Roperto
author_sort	Sante Roperto
title	Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
title_short	Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
title_full	Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
title_fullStr	Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
title_full_unstemmed	Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
title_sort	bovine papillomavirus type 2 (bpv-2) e5 oncoprotein binds to the subunit d of the v₁-atpase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ae1628fdd3ee4c9a929fde3176194580
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Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.

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