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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)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Apoptosis ; Arginine Methylation ; Pancreatic Cancer ; Post-translational Modification ; Tumor Suppression; Protein Arginine-methyltransferase; Arf; Methylation; Binding; P53; Nucleolar; Phosphorylation; Localization; Stability; Phenotype
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Journal EMBO Journal, The
Quellenangaben Volume: , Issue: , Pages: e106777 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Heidelberg, Germany
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
Institute of Diabetes and Obesity (IDO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Helmholtz Diabetes Center
PSP Element(s) G-501760-001
G-502200-001
Grants Deutsche Forschungsgemeinschaft (DFG)
DOI 10.15252/embj.2020106777
WOS ID WOS:000651125000001
Scopus ID 85105773985
PubMed ID 33999432
Erfassungsdatum 2021-05-25
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