| Autor: |
Stephen Henderson, Alma L. Burlingame, Marta Munoz-Alegre, Alexander Hergovich, A. E. Roehrigh, Juan A. Oses-Prieto, Pablo Rodriguez-Viciana, A. Blees, K. Klupsch, Barbara H. Jennings, Nicole Hartig, Warren Emmett, Silvia Surinova, F. Brunk, A. Pfeiffer, S. Chaib, Maha Tijani, Lucy C. Young |
| Rok vydání: |
2019 |
| Předmět: |
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| Popis: |
SUMMARYThe PAF complex (PAFC) coordinates transcription elongation and mRNA processing events and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions at the cell cortex and nucleus and is a key mediator of contact inhibition. Here we provide a direct link between nuclear Merlin and transcription elongation controlled by cell-cell adhesion. Merlin interacts with the PAFC in a cell density-dependent manner and tumour-derived inactivating mutations in both Merlin and CDC73 mutually disrupt their interaction. Growth suppression by Merlin requires CDC73 and Merlin regulates PAFC association with chromatin in a subset of genes. We also identify by CDC73 affinity-proteomics a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, nuclear Merlin is part of a tumour suppressor network which coordinates postinitiation steps of the transcription cycle of genes mediating in contact inhibition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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