Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
PLoS One
; 16(8): e0254697, 2021.
Article
em En
| MEDLINE
| ID: mdl-34424918
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adesão Celular
/
DNA Helicases
/
Neurofibromina 2
/
Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article