p33(ING1b) stimulates the transcriptional activity of the estrogen receptor alpha via its activation function (AF) 2 domain.
The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer, and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigated whether p33(ING1b), one of the major ING1 isoforms, modulated the transcriptional activity of estrogen receptor (ER) alpha. In Cos-7 cells transfected with increasing concentrations of a mammalian expression vector encoding for p33(ING1b), estrogen-induced ERalpha transcriptional activity was found to increase in a dose-dependent manner. As p33(ING1b) expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ERalpha or activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33(ING1b). These results showed that p33(ING1b) enhanced estrogen-induced ERalpha activity through the AF2 domain. Our data also demonstrated that the antiestrogens inhibited the transcriptional activity of ERalpha as stimulated by p33(ING1b). Furthermore, a weak physical association was observed between in vitro translated p33(ING1b) and ERalpha. Our data presented here demonstrate that p33(ING1b) acts like a coactivator for ERalpha and stimulates estrogen-induced ERalpha transcriptional activity consistent with a function for p33(ING1b) in chromatin remodeling.
Toyama
Tatsuya
T
Department of Surgery II, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. toyamat-ncu@umin.ac.jp
Iwase
Hirotaka
H
Yamashita
Hiroko
H
Hara
Yasuo
Y
Sugiura
Hiroshi
H
Zhang
Zhenhuan
Z
Fukai
Ichiro
I
Miura
Yutaka
Y
Riabowol
Karl
K
Fujii
Yoshitaka
Y
D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D006388:Hemagglutinins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D008156:Luciferases