Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells.
In previous studies we have shown that all-trans retinoic acid (atRA)-treatment of the atRA-sensitive ovarian carcinoma cell line CA-OV3 repressed AP-1 activity by about 50%, while a similar effect was not observed in the atRA-resistant ovarian carcinoma cell line, SK-OV3. These results suggested that the repression of AP-1 activity may be one of the mechanisms by which atRA inhibits the growth of atRA-sensitive CA-OV3 cells. In the present studies, we investigated further the molecular mechanism by which AP-1 activity is repressed by atRA. We show that the repression of AP-1 activity correlates with an increase in JunB protein expression and a decrease in N-terminal phosphorylation of c-Jun. The decrease in N-terminal phosphorylation of c-Jun does not appear to be modulated by JNK or ERK, since their protein expression patterns and kinase activity do not correlate with the repression of AP-1 activity following treatment with atRA. However, the activity of the protein phosphatase PP2A was found to increase 24 h following atRA treatment in CA-OV3 cells. Moreover, the catalytic subunit of PP2A was found to associate with c-Jun in vivo following atRA treatment. Since the inhibition of AP-1 activity following atRA treatment of CA-OV3 cells was abolished in the presence of specific PP2A inhibitors, it is likely that PP2A plays an important role in the atRA-induced repression of AP-1.
Ramírez
Carmilia Jiménez
CJ
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
Haberbusch
Juliet M
JM
Soprano
Dianne Robert
DR
Soprano
Kenneth J
KJ
D002277:Carcinoma / Q000201:enzymology*; D045744:Cell Line, Tumor; D019281:Dimerization; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014212:Tretinoin / Q000502:physiology*
D018808:Transcription Factor AP-1; D012694:Serine; D014212:Tretinoin; D048031:JNK Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases