title: PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity.
abstract: The proto-oncogene c-Jun is a component of activator protein-1 (AP-1) transcription factor complexes that regulates processes essential for embryonic development, tissue homeostasis and malignant transformation. Induction of gene expression by c-Jun involves stimulation of its transactivation ability and upregulation of DNA binding capacity. While it is well established that the former requires JNK-mediated phosphorylation of S63/S73, the mechanism(s) through which binding of c-Jun to its endogenous target genes is regulated remains poorly characterized. Here we show that interaction of c-Jun with chromatin is positively regulated by protein phosphatase 2A (PP2A) complexes targeted to c-Jun by the PR55α regulatory subunit. PR55α-PP2A specifically dephosphorylates T239 of c-Jun, promoting its binding to genes regulating tumour cell migration and invasion. PR55α-PP2A also enhanced transcription of these genes, without affecting phosphorylation of c-Jun on S63. These findings suggest a critical role for interplay between JNK and PP2A pathways determining the functional activity of c-Jun/AP-1 in tumour cells.
authors.affiliation: 1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: O
authors.initials: O
authors.lastname: Gilan
authors.affiliation: 1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Diesch
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Amalia
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Jastrzebski
authors.affiliation: Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia.
authors.forename: A C
authors.identifier: 0000000311405516
authors.initials: AC
authors.lastname: Chueh
authors.affiliation: 1] School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia [2] Hunter Medical Research Institute, New Lambton, New South Wales, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Verrills
authors.affiliation: 1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia [3] Sir Peter MacCallum Department of Oncology, University of Melbourne, East Melbourne, Victoria, Australia [4] Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: R B
authors.initials: RB
authors.lastname: Pearson
authors.affiliation: Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Mariadason
authors.affiliation: Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
authors.forename: E
authors.initials: E
authors.lastname: Tulchinsky
authors.affiliation: 1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia [3] Sir Peter MacCallum Department of Oncology, University of Melbourne, East Melbourne, Victoria, Australia [4] Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia [5] School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: R D
authors.initials: RD
authors.lastname: Hannan
authors.affiliation: 1] Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, East Melbourne, Victoria, Australia [3] Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: A S
authors.initials: AS
authors.lastname: Dhillon
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D000099169:Fos-Related Antigen 1
chemical_list: D054648:Protein Phosphatase 2; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1; C000715470:MAS1 protein, human; C512974:PPP2R2A protein, human