TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malig...

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Autores principales:	Adrien Rousseau, Alastair G McEwen, Pierre Poussin-Courmontagne, Didier Rognan, Yves Nominé, Marie-Christine Rio, Catherine Tomasetto, Fabien Alpy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b8771cce77cd4992a489c9c52e0fecfd
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spelling	oai:doaj.org-article:b8771cce77cd4992a489c9c52e0fecfd2021-11-18T05:37:42ZTRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.1544-91731545-788510.1371/journal.pbio.1001726https://doaj.org/article/b8771cce77cd4992a489c9c52e0fecfd2013-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24311986/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.Adrien RousseauAlastair G McEwenPierre Poussin-CourmontagneDidier RognanYves NominéMarie-Christine RioCatherine TomasettoFabien AlpyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 12, p e1001726 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Adrien Rousseau Alastair G McEwen Pierre Poussin-Courmontagne Didier Rognan Yves Nominé Marie-Christine Rio Catherine Tomasetto Fabien Alpy TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
description	Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.
format	article
author	Adrien Rousseau Alastair G McEwen Pierre Poussin-Courmontagne Didier Rognan Yves Nominé Marie-Christine Rio Catherine Tomasetto Fabien Alpy
author_facet	Adrien Rousseau Alastair G McEwen Pierre Poussin-Courmontagne Didier Rognan Yves Nominé Marie-Christine Rio Catherine Tomasetto Fabien Alpy
author_sort	Adrien Rousseau
title	TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
title_short	TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
title_full	TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
title_fullStr	TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
title_full_unstemmed	TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
title_sort	traf4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b8771cce77cd4992a489c9c52e0fecfd
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TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.

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