Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.
Cell Adhesion
/ genetics
Cell Proliferation
/ genetics
Chromatin
/ genetics
Chromatin Assembly and Disassembly
/ genetics
Contact Inhibition
/ genetics
DNA Helicases
/ genetics
DNA-Binding Proteins
/ genetics
Gene Expression Regulation
/ genetics
HEK293 Cells
Humans
Neoplasms
/ genetics
Neurofibromin 2
/ genetics
Protein Binding
/ genetics
Protein Interaction Maps
/ genetics
Signal Transduction
/ genetics
Tumor Suppressor Proteins
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
11
09
2020
accepted:
01
07
2021
entrez:
23
8
2021
pubmed:
24
8
2021
medline:
25
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34424918
doi: 10.1371/journal.pone.0254697
pii: PONE-D-20-28670
pmc: PMC8382200
doi:
Substances chimiques
CDC73 protein, human
0
Chromatin
0
DNA-Binding Proteins
0
Neurofibromin 2
0
Tumor Suppressor Proteins
0
DNA Helicases
EC 3.6.4.-
CHD1 protein, human
EC 3.6.4.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0254697Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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