- Title
- PR55α-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity
- Creator
- Gilan, O.; Diesch, J.; Dhillon, A. S.; Amalia, M.; Jastrzebski, K.; Chueh, A. C.; Verrills, N. M.; Pearson, R. B.; Mariadason, J. M.; Tulchinsky, E.; Hannan, R. D.
- Relation
- Oncogene Vol. 34, Issue 10, p. 1333-1339
- Publisher Link
- http://dx.doi.org/10.1038/onc.2014.26
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- PR55α; protein phosphatase 2A; cancer cells; tumour cells
- Identifier
- http://hdl.handle.net/1959.13/1338167
- Identifier
- uon:27953
- Identifier
- ISSN:1476-5594
- Language
- eng
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