p33ING1b and estrogen receptor (ER) alpha.
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). Both CREB binding protein (CBP) and the related p300 proteins show a marked preference for binding to complexes containing p33ING1b, one of the major ING1 isoforms, whereas HDAC immunocomplexes contain equal amounts of p33ING1b and p47ING1a. This observation is interesting, given that p33ING1b can selectively increase histone H3 and H4 acetylation when micro-injected into individual cells, whereas p47ING1a inhibits histone acetylation. We investigated whether p33ING1b modulated the transcriptional activity of estrogen receptor (ER)alpha. In cells transfected with increasing concentrations of a mammalian expression vector encoding p33ING1b, estrogen-induced ER alpha transcriptional activity was found to increase in a dose-dependent manner. As p33ING1b expression levels increased, transcription of an ER-responsive reporter gene by either estrogen-inducible full-length ER alpha or the activation function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was unaffected by the presence of p33ING1b. These results showed that p33ING1b enhanced estrogen-induced ER alpha activity through the AF2 domain. Our data demonstrate that p33ING1b acts like a coactivator for ER alpha and stimulates estrogen-induced ER alpha transcriptional activity consistent with a function for p33ING1b in chromatin remodeling.
Toyama
Tatsuya
T
Department of Breast Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. toyamat-ncu@umin.ac.jp
Iwase
Hirotaka
H
D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000235:genetics*; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006131:Growth Inhibitors / Q000235:genetics*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D006131:Growth Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011960:Receptors, Estrogen; D025521:Tumor Suppressor Proteins