| Title: |
PRMT1 promotes the tumor suppressor function of p14 ARF and is indicative for pancreatic cancer prognosis. |
| Authors: |
Repenning, A.; Happel, D.; Bouchard, C.; Meixner, M.; Verel-Yilmaz, Y.; Raifer, H.; Holembowski, L.; Krause, E.; Kremmer, E.; Feederle, R.; Keber, C.U.; Lohoff, M.; Slater, E.P.; Bartsch, D.K.; Bauer, U.M. |
| Source: |
EMBO J., e106777 (2021) |
| Publisher Information: |
Wiley |
| Publication Year: |
2021 |
| Collection: |
PuSH - Publikationsserver des Helmholtz Zentrums München |
| Subject Terms: |
Apoptosis; Arginine Methylation; Pancreatic Cancer; Post-translational Modification; Tumor Suppression |
| Description: |
The p14 protein is a well-known regulator of p53-dependent and p53-independent tumor-suppressive activities. In unstressed cells, p14 is predominantly sequestered in the nucleoli, bound to its nucleolar interaction partner NPM. Upon genotoxic stress, p14 undergoes an immediate redistribution to the nucleo- and cytoplasm, where it promotes activation of cell cycle arrest and apoptosis. Here, we identify p14 as a novel interaction partner and substrate of PRMT1 (protein arginine methyltransferase 1). PRMT1 methylates several arginine residues in the C-terminal nuclear/nucleolar localization sequence (NLS/NoLS) of p14 . In the absence of cellular stress, these arginines are crucial for nucleolar localization of p14 . Genotoxic stress causes augmented interaction between PRMT1 and p14 , accompanied by arginine methylation of p14 . PRMT1-dependent NLS/NoLS methylation promotes the release of p14 from NPM and nucleolar sequestration, subsequently leading to p53-independent apoptosis. This PRMT1-p14 cooperation is cancer-relevant and indicative for PDAC (pancreatic ductal adenocarcinoma) prognosis and chemotherapy response of pancreatic tumor cells. Our data reveal that PRMT1-mediated arginine methylation is an important trigger for p14 ’s stress-induced tumor-suppressive function. ARF ARF ARF ARF ARF ARF ARF ARF ARF ARF ARF |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/33999432; info:eu-repo/semantics/altIdentifier/wos/WOS:000651125000001; info:eu-repo/semantics/altIdentifier/isbn/0261-4189; info:eu-repo/semantics/a |
| DOI: |
10.15252/embj.2020106777 |
| Availability: |
https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=62056; https://doi.org/10.15252/embj.2020106777 |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.5C08E027 |
| Database: |
BASE |