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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.*

PRMT1 promotes the tumor suppressor function of p14ARF and is indicative for pancreatic cancer prognosis.

EMBO J., e106777 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apoptosis ; Arginine Methylation ; Pancreatic Cancer ; Post-translational Modification ; Tumor Suppression; Protein Arginine-methyltransferase; Arf; Methylation; Binding; P53; Nucleolar; Phosphorylation; Localization; Stability; Phenotype
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: , Heft: , Seiten: e106777 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Institute of Diabetes and Obesity (IDO)
Förderungen Deutsche Forschungsgemeinschaft (DFG)