Journal Article


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

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.

Attached files

Authors

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

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2021
Date of RADAR deposit: 2022-08-17


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License


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