Roehrig, AE;
Klupsch, K;
Oses-Prieto, JA;
Chaib, S;
Henderson, S;
Emmett, W;
Young, LC;
... Rodriguez-Viciana, P; + view all
(2021)
Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
PLoS One
, 16
(8)
, Article e0254697. 10.1371/journal.pone.0254697.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0254697 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0254697 |
| Language: | English |
| Additional information: | © 2021 Roehrig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10134493 |
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