Poster Presentation 26th Lorne Cancer Conference 2014

A PR55a-containing PP2A complex positively regulates Fra-1/c-Jun function in tumour cells (#152)

Omer Gilan 1 , Jeannine Diesch 1 , Marcia Amalia 1 , Katarzyna Jastrzebski 1 , Anderly Chueh 2 , Nicole M Verrills 3 4 , Richard B Pearson 1 , John M Mariadason 2 , Eugene Tulchinsky 5 , Ross D Hannan 1 , Amardeep S Dhillon 1
  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  2. Research, Ludwig Institute for Cancer Research, Melbourne, VIC, Australia
  3. School of Biolmedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia
  4. Hunter Medical Research Institute, New Lambton, NSW, Australia
  5. Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom

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 characterised. Here we shown 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 is determining the functional activity of c-Jun/AP-1 in tumour cells.