KMID : 0578320090280010067
|
|
Molecules and Cells 2009 Volume.28 No. 1 p.67 ~ p.71
|
|
PKA-Mediated stabilization of FoxH1 negatively regulates ER¥á activity
|
|
Yum Jin-Ah
Jeong Hyung-Min Kim Seul-Ki Seo Jin-Won Han Youn-Ho Lee Kwang-Youl Yeo Chang-Yeol
|
|
Abstract
|
|
|
Estrogen receptor ¥á (ER¥á) mediates the mitogenic effects of estrogen. ER¥á signaling regulates the normal growth and differentiation of mammary tissue, but uncontrolled ER¥á activation increases the risk to breast cancer. Estrogen binding induces ligand-dependent ER¥á activation, thereby facilitating ER¥á dimerization, promoter binding and coactivator recruitment. ER¥á can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling. However, in several ER¥á-positive breast cancer cells, PKA inhibits estrogen-dependent cell growth. FoxH1 represses the transcriptional activities of estrogen receptors and androgen receptors (AR). Interestingly, FoxH1 has been found to inhibit the PKA-induced and ligand-induced activation of AR. In the present study, we examined the effects of PKA activation on the ability of FoxH1 to represses ER¥á transcriptional activity. We found that PKA increases the protein stability of FoxH1, and that FoxH1 inhibits PKA-induced and estradiol-induced activation of an estrogen response element (ERE). Furthermore, in MCF7 cells, FoxH1 knockdown increased the PKA-induced and estradiol-induced activation of the ERE. These results suggest that PKA can negatively regulate ER¥á, at least in part, through FoxH1.
|
|
KEYWORD
|
|
estrogen receptor ¥á, FoxH1, protein kinase A, protein stability
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|