Premium
Retinoic acid induced repression of AP‐1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells
Author(s) -
Ramírez Carmilia Jiménez,
Haberbusch Juliet M.,
Soprano Dianne Robert,
Soprano Kenneth J.
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20520
Subject(s) - psychological repression , protein phosphatase 2 , junb , retinoic acid , phosphatase , phosphorylation , cycloheximide , chemistry , mapk/erk pathway , protein subunit , cell culture , microbiology and biotechnology , biology , biochemistry , protein biosynthesis , gene expression , gene , genetics
In previous studies we have shown that all ‐ trans retinoic acid ( at RA)‐treatment of the at RA‐sensitive ovarian carcinoma cell line CA‐OV3 repressed AP‐1 activity by about 50%, while a similar effect was not observed in the at RA‐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 at RA inhibits the growth of at RA‐sensitive CA‐OV3 cells. In the present studies, we investigated further the molecular mechanism by which AP‐1 activity is repressed by at RA. 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 at RA. However, the activity of the protein phosphatase PP2A was found to increase 24 h following at RA treatment in CA‐OV3 cells. Moreover, the catalytic subunit of PP2A was found to associate with c‐Jun in vivo following at RA treatment. Since the inhibition of AP‐1 activity following at RA 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 at RA‐induced repression of AP‐1. © 2005 Wiley‐Liss, Inc.