PRMT1 Is Critical for the Transcriptional Activity and the Stability of the Progesterone Receptor.
The progesterone receptor (PR) is an inducible transcription factor that playscritical roles in female reproductive processes and in several aspects of breastcancer tumorigenesis. Our report describes the type I protein argininemethyltransferase 1 (PRMT1) as a cofactor controlling progesterone pathway, throughthe direct methylation of PR. Mechanistic assays in breast cancer cells indicatethat PRMT1 methylates PR at the arginine 637 and reduces the stability of thereceptor, thereby accelerating its recycling and finally its transcriptionalactivity. Depletion of PRMT1 decreases the expression of a subset ofprogesterone-inducible genes, controlling breast cancer cells proliferation andmigration. Consistently, Kaplan-Meier analysis revealed that low expression of PRMT1predicts a longer survival among the subgroup with high PR. Our study highlights PRmethylation as a molecular switch adapting the transcription requirement of breastcells during tumorigenesis.
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