Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
- Resource Type
- Article
- 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
- Source
- PLoS ONE. 8/23/2021, Vol. 16 Issue 8, p1-31. 31p.
- Subject
- *CONTACT inhibition
*CELL adhesion
*CELL nuclei
*CADHERINS
*CELL physiology
*PROTEOMICS
- Language
- ISSN
- 1932-6203
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. [ABSTRACT FROM AUTHOR]