p53 down-regulates ER-responsive genes by interfering with the binding of ER to ERE.
Overexpression of the tumor suppressor p53 in HeLa cells leads to loss of the estradiol- and genistein-induced human estrogen receptor (ERalpha) transactivity. The coactivator p300, which binds to both ERalpha and p53, does not prevent this loss of hERalpha function. In this report we demonstrate that p53 physically binds to multiple domains of the hERalpha. This binding did not interfere with either the ERalpha dimerization or the interaction between hERalpha and its coactivator SRC-1. However, p53 did interfere with the hERalpha-ERE binding. These results may explain how p53 down-regulates the expression of some estrogen-responsive genes such as c-fos, c-jun, TPA, and bcl-2. This study supports the cross-talk between the p53 and the ERalpha signaling pathways.
Liu
G
G
Graduate Program in Cancer Biology, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA.
Schwartz
J A
JA
Brooks
S C
SC
D019281:Dimerization; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000494:pharmacology; D056920:Nuclear Receptor Coactivator 1; D010957:Plasmids; D014176:Protein Biosynthesis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D019833:Genistein; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1