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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382200/ https://www.ncbi.nlm.nih.gov/pubmed/34424918 http://dx.doi.org/10.1371/journal.pone.0254697 |
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author | Roehrig, Anne E. Klupsch, Kristina Oses-Prieto, Juan A. Chaib, Selim Henderson, Stephen Emmett, Warren Young, Lucy C. Surinova, Silvia Blees, Andreas Pfeiffer, Anett Tijani, Maha Brunk, Fabian Hartig, Nicole Muñoz-Alegre, Marta Hergovich, Alexander Jennings, Barbara H. Burlingame, Alma L. Rodriguez-Viciana, Pablo |
author_facet | Roehrig, Anne E. Klupsch, Kristina Oses-Prieto, Juan A. Chaib, Selim Henderson, Stephen Emmett, Warren Young, Lucy C. Surinova, Silvia Blees, Andreas Pfeiffer, Anett Tijani, Maha Brunk, Fabian Hartig, Nicole Muñoz-Alegre, Marta Hergovich, Alexander Jennings, Barbara H. Burlingame, Alma L. Rodriguez-Viciana, Pablo |
author_sort | Roehrig, Anne E. |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8382200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83822002021-08-24 Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex Roehrig, Anne E. Klupsch, Kristina Oses-Prieto, Juan A. Chaib, Selim Henderson, Stephen Emmett, Warren Young, Lucy C. Surinova, Silvia Blees, Andreas Pfeiffer, Anett Tijani, Maha Brunk, Fabian Hartig, Nicole Muñoz-Alegre, Marta Hergovich, Alexander Jennings, Barbara H. Burlingame, Alma L. Rodriguez-Viciana, Pablo PLoS One Research Article 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. Public Library of Science 2021-08-23 /pmc/articles/PMC8382200/ /pubmed/34424918 http://dx.doi.org/10.1371/journal.pone.0254697 Text en © 2021 Roehrig et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Roehrig, Anne E. Klupsch, Kristina Oses-Prieto, Juan A. Chaib, Selim Henderson, Stephen Emmett, Warren Young, Lucy C. Surinova, Silvia Blees, Andreas Pfeiffer, Anett Tijani, Maha Brunk, Fabian Hartig, Nicole Muñoz-Alegre, Marta Hergovich, Alexander Jennings, Barbara H. Burlingame, Alma L. Rodriguez-Viciana, Pablo Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex |
title | 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_short | Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex |
title_sort | cell-cell adhesion regulates merlin/nf2 interaction with the paf complex |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382200/ https://www.ncbi.nlm.nih.gov/pubmed/34424918 http://dx.doi.org/10.1371/journal.pone.0254697 |
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