All-trans- and 9-cis-retinoic acids activate the human cyclooxynase-2 gene: a role for DR1 as RARE or RXRE

作者：Han Kyuyong; Moon Irene; Lim Hyunjung J^*

来源：Molecular Biology Reports, 2011, 38(2): 833-840.

DOI：10.1007/s11033-010-0173-4

• COX-2
• PPAR delta
• RAR
• RXR
• DR1
• Retinoic acids

The human COX-2 promoter contains a direct repeat 1 (DR1) which was shown to confer responsiveness to PPARs. We found that in AN(3)CA and F9 cells, this hCOX-2 DR1 mediates responsiveness to all-trans-retinoic acid (tRA) or 9-cis-retinoic acid (9cRA), but this effect was suppressed by PPAR delta. Truncated PPAR delta lacking the activation domain AF2 cannot suppress RA-induced activation of the hCOX-2 gene via DR1, suggesting that cofactor recruitment by AF2 is required for the suppression by PPAR delta. Gel shift assay showed that PPAR/RXR, RAR beta/RXR, and RXR/RXR, bind to hCOX-2 DR1, revealing the promiscuity of this DR1. Particularly, RXR homodimer was able to bind to this DR1 only in the presence of 9cRA. Our results established that tRA and 9cRA are potent inducers of hCOX-2 and that the hCOX-2 DR1 could either serve as RARE or RXRE depending on cellular contexts.

• 出版日期2011-2