title: Identification of the PRMT1v1 and PRMT1v2 specific interactomes by quantitative mass spectrometry in breast cancer cells.
abstract: Arginine methylation is catalyzed by a family of enzymes called protein arginine methyltransferases (PRMTs). The PRMT1 gene generates at least seven distinct alternatively spliced isoforms (PRMT v1-v7), which together contribute a significant portion of the cellular arginine methylome. The distinct biochemical and biological functions of these PRMT1 isoforms have not been well characterized. Previously we have shown that while both PRMT1v1 and PRMT1v2 are overexpressed in breast cancer cells, PRMT1v2 specifically promotes breast cancer cell survival and invasion. These isoforms also have distinct subcellular localizations, PRMT1v1 is mainly nuclear and PRMT1v2 cytosolic. To gain further knowledge into their isoform-specific roles within cells we used a SILAC-based quantitative affinity purification/MS approach to identify their individual protein interactomes in breast cancer cells. This analysis has uncovered distinct interactomes for PRMT1v1 and PRMT1v2. Consistent with their distinct subcellular localizations, PRMT1v1 enriched a mainly nuclear protein interactome, while PRMT1v2 enriched predominantly cytoplasmic interactors from whole-cell extracts. Furthermore, these interactomes revealed that PRMT1v1 has a role in regulating gene expression, while PRMT1v2 functions in cytoskeletal dynamics. These results highlight the unique functions of these isoforms and the distinct roles they may play within cells, with potential implications for breast cancer and other diseases.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.|Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: R Mitchell
authors.initials: RM
authors.lastname: Baldwin
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.|Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Bejide
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.|Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Trinkle-Mulcahy
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.|Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Côté
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012097:Repressor Proteins; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: Arginine methylation; Breast cancer; PRMT; Quantitative mass spectrometry; SILAC