Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.

Protein transduction offers a great therapeutic potential by efficient delivery of biologically active cargo into cells. The Adenovirus Dd (Dodecahedron) has recently been shown to deliver proteins fused to the tandem WW(2-3-4) structural domains from the E3 ubiquitin ligase Nedd4. In this study, we...

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Autores principales:	Ana Villegas-Méndez, Pascal Fender, Marina I Garin, Romy Rothe, Lavinia Liguori, Bruno Marques, Jean-Luc Lenormand
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a441a9e95964defaeaa1895be2f9368
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spelling	oai:doaj.org-article:8a441a9e95964defaeaa1895be2f93682021-11-18T07:04:12ZFunctional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.1932-620310.1371/journal.pone.0045416https://doaj.org/article/8a441a9e95964defaeaa1895be2f93682012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028993/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Protein transduction offers a great therapeutic potential by efficient delivery of biologically active cargo into cells. The Adenovirus Dd (Dodecahedron) has recently been shown to deliver proteins fused to the tandem WW(2-3-4) structural domains from the E3 ubiquitin ligase Nedd4. In this study, we conclusively show that Dd is able to efficiently deliver cargo inside living cells, which mainly localize in fast moving endocytic vesicles, supporting active transport along the cytoskeleton. We further improve this delivery system by expressing a panel of 13 WW-GFP mutant forms to characterize their binding properties towards Dd. We identified the domain WW(3) and its mutant form WW(3)_10_13 to be sufficient for optimal binding to Dd. We greatly minimise the interacting WW modules from 20 to 6 kDa without compromising its efficient delivery by Dd. Using these minimal WW domains fused to the tumor suppressor p53 protein, we show efficient cellular uptake and distribution into cancer cells, leading to specific induction of apoptosis in these cells. Taken together, these findings represent a step further towards the development of a Dd-based delivery system for future therapeutic application.Ana Villegas-MéndezPascal FenderMarina I GarinRomy RotheLavinia LiguoriBruno MarquesJean-Luc LenormandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45416 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Villegas-Méndez Pascal Fender Marina I Garin Romy Rothe Lavinia Liguori Bruno Marques Jean-Luc Lenormand Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
description	Protein transduction offers a great therapeutic potential by efficient delivery of biologically active cargo into cells. The Adenovirus Dd (Dodecahedron) has recently been shown to deliver proteins fused to the tandem WW(2-3-4) structural domains from the E3 ubiquitin ligase Nedd4. In this study, we conclusively show that Dd is able to efficiently deliver cargo inside living cells, which mainly localize in fast moving endocytic vesicles, supporting active transport along the cytoskeleton. We further improve this delivery system by expressing a panel of 13 WW-GFP mutant forms to characterize their binding properties towards Dd. We identified the domain WW(3) and its mutant form WW(3)_10_13 to be sufficient for optimal binding to Dd. We greatly minimise the interacting WW modules from 20 to 6 kDa without compromising its efficient delivery by Dd. Using these minimal WW domains fused to the tumor suppressor p53 protein, we show efficient cellular uptake and distribution into cancer cells, leading to specific induction of apoptosis in these cells. Taken together, these findings represent a step further towards the development of a Dd-based delivery system for future therapeutic application.
format	article
author	Ana Villegas-Méndez Pascal Fender Marina I Garin Romy Rothe Lavinia Liguori Bruno Marques Jean-Luc Lenormand
author_facet	Ana Villegas-Méndez Pascal Fender Marina I Garin Romy Rothe Lavinia Liguori Bruno Marques Jean-Luc Lenormand
author_sort	Ana Villegas-Méndez
title	Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
title_short	Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
title_full	Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
title_fullStr	Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
title_full_unstemmed	Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
title_sort	functional characterisation of the ww minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8a441a9e95964defaeaa1895be2f9368
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Functional characterisation of the WW minimal domain for delivering therapeutic proteins by adenovirus dodecahedron.

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