PR55a-containing protein phosphatase 2A complexes promote cancer cell migration and invasion through regulation of AP-1 transcriptional activity

Date

2015

Authors

Gilan, Omer
Diesch, Jeannine
Amalia, Marcia
Jastrzebski, Katarzyna
Chueh, A C
Verrills, N M
Pearson, Richard B
Mariadason, J M
Tulchinsky, Eugene
Hannan, Ross

Journal Title

Journal ISSN

Volume Title

Publisher

Nature Publishing Group

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.

Description

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Citation

Source

Oncogene

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1038/onc.2014.26

Restricted until

2037-12-31