PRMT1 Is Critical for the Transcriptional Activity and the Stability of the Progesterone Receptor
Lucie Malbeteau,
Coralie Poulard,
Cécile Languilaire,
Ivan Mikaelian,
Frédéric Flamant,
Muriel Le Romancer,
Laura Corbo
Affiliations
Lucie Malbeteau
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France
Coralie Poulard
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France
Cécile Languilaire
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France
Ivan Mikaelian
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France
Frédéric Flamant
Université Lyon 1, Lyon F-69000, France; Institut de Génomique Fonctionnelle de Lyon, INRA USC 1370, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, Lyon Cedex 07, France
Muriel Le Romancer
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France; Corresponding author
Laura Corbo
Université Lyon 1, Lyon F-69000, France; Inserm U1052 CNRS UMR 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon F-69008, France; Corresponding author
Summary: The progesterone receptor (PR) is an inducible transcription factor that plays critical roles in female reproductive processes and in several aspects of breast cancer tumorigenesis. Our report describes the type I protein arginine methyltransferase 1 (PRMT1) as a cofactor controlling progesterone pathway, through the direct methylation of PR. Mechanistic assays in breast cancer cells indicate that PRMT1 methylates PR at the arginine 637 and reduces the stability of the receptor, thereby accelerating its recycling and finally its transcriptional activity. Depletion of PRMT1 decreases the expression of a subset of progesterone-inducible genes, controlling breast cancer cells proliferation and migration. Consistently, Kaplan-Meier analysis revealed that low expression of PRMT1 predicts a longer survival among the subgroup with high PR. Our study highlights PR methylation as a molecular switch adapting the transcription requirement of breast cells during tumorigenesis.