Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms...

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Autores principales:	Anne E Roehrig, Kristina Klupsch, Juan A Oses-Prieto, Selim Chaib, Stephen Henderson, Warren Emmett, Lucy C Young, Silvia Surinova, Andreas Blees, Anett Pfeiffer, Maha Tijani, Fabian Brunk, Nicole Hartig, Marta Muñoz-Alegre, Alexander Hergovich, Barbara H Jennings, Alma L Burlingame, Pablo Rodriguez-Viciana
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/060b7e02b03d49888281c2e401c2133d
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spelling	oai:doaj.org-article:060b7e02b03d49888281c2e401c2133d2021-12-02T20:17:40ZCell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.1932-620310.1371/journal.pone.0254697https://doaj.org/article/060b7e02b03d49888281c2e401c2133d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254697https://doaj.org/toc/1932-6203The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.Anne E RoehrigKristina KlupschJuan A Oses-PrietoSelim ChaibStephen HendersonWarren EmmettLucy C YoungSilvia SurinovaAndreas BleesAnett PfeifferMaha TijaniFabian BrunkNicole HartigMarta Muñoz-AlegreAlexander HergovichBarbara H JenningsAlma L BurlingamePablo Rodriguez-VicianaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254697 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anne E Roehrig Kristina Klupsch Juan A Oses-Prieto Selim Chaib Stephen Henderson Warren Emmett Lucy C Young Silvia Surinova Andreas Blees Anett Pfeiffer Maha Tijani Fabian Brunk Nicole Hartig Marta Muñoz-Alegre Alexander Hergovich Barbara H Jennings Alma L Burlingame Pablo Rodriguez-Viciana Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
description	The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.
format	article
author	Anne E Roehrig Kristina Klupsch Juan A Oses-Prieto Selim Chaib Stephen Henderson Warren Emmett Lucy C Young Silvia Surinova Andreas Blees Anett Pfeiffer Maha Tijani Fabian Brunk Nicole Hartig Marta Muñoz-Alegre Alexander Hergovich Barbara H Jennings Alma L Burlingame Pablo Rodriguez-Viciana
author_facet	Anne E Roehrig Kristina Klupsch Juan A Oses-Prieto Selim Chaib Stephen Henderson Warren Emmett Lucy C Young Silvia Surinova Andreas Blees Anett Pfeiffer Maha Tijani Fabian Brunk Nicole Hartig Marta Muñoz-Alegre Alexander Hergovich Barbara H Jennings Alma L Burlingame Pablo Rodriguez-Viciana
author_sort	Anne E Roehrig
title	Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
title_short	Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
title_full	Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
title_fullStr	Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
title_full_unstemmed	Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
title_sort	cell-cell adhesion regulates merlin/nf2 interaction with the paf complex.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/060b7e02b03d49888281c2e401c2133d
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Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.

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