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  • Original Article
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PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity

Oncogene volume 34, pages 1333–1339 (2015)Cite this article

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A Corrigendum to this article was published on 05 March 2015

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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.

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  • 05 March 2015

    This article has been corrected since Advance Online Publication and a corrigendum is also printed in this issue

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Acknowledgements

We thank Drs David Gillespie, Eisuke Nishida, Chunming Liu, Kanaga Sabapathy and William Kaelin for providing reagents used in this study. This work was supported by project grants (to ASD and RDH) and Research Fellowships (to RDH, RBP and JMM) from the National Health and Medical Research Council of Australia and the Cancer Institute NSW (to NMV).

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Authors and Affiliations

  1. Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia,

    O Gilan, J Diesch, M Amalia, K Jastrzebski, R B Pearson, R D Hannan & A S Dhillon

  2. Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia,

    O Gilan, J Diesch, R B Pearson & R D Hannan

  3. Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia

    A C Chueh & J M Mariadason

  4. School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia,

    N M Verrills

  5. Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    N M Verrills

  6. Sir Peter MacCallum Department of Oncology, University of Melbourne, East Melbourne, Victoria, Australia,

    R B Pearson, R D Hannan & A S Dhillon

  7. Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    R B Pearson & R D Hannan

  8. Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK,

    E Tulchinsky

  9. School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia

    R D Hannan

  10. Department of Pathology, University of Melbourne, Parkville, Victoria, Australia

    A S Dhillon

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  1. O Gilan
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Correspondence to A S Dhillon.

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Gilan, O., Diesch, J., Amalia, M. et al. PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity. Oncogene 34, 1333–1339 (2015). https://doi.org/10.1038/onc.2014.26

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  • DOI: https://doi.org/10.1038/onc.2014.26

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