Concerted activation of ETS protein ER81 by p160 coactivators, the acetyltransferase p300 and the receptor tyrosine kinase HER2/Neu.
Activator of thyroid and retinoic acid receptor (ACTR) is overexpressed in approximately 60% of primary human breast tumors and belongs to the p160 steroid receptor coactivator family. In this study, we identified a novel interaction partner of ACTR, the ETS transcription factor ER81 that is also heavily implicated in mammary ... tumor formation. ACTR and related p160 family members (steroid receptor coactivator-1 and glucocorticoid receptor-interacting protein-1 (GRIP-1)) augment ER81-mediated transcription. Although ACTR and GRIP-1 can acetylate ER81, this posttranslational modification of ER81 is not required for its stimulation by ACTR or GRIP-1. In addition, ACTR collaborates with the p300 coactivator, a joint interaction partner of ACTR and ER81, to stimulate ER81 function and the ability of p300 to acetylate ER81 is indispensable for this collaboration. Furthermore, the receptor tyrosine kinase HER2/Neu, an oncoprotein particularly found overexpressed in breast tumors, cooperates with both ACTR and p300 to stimulate ER81-mediated transcription. Thus, oncogenic HER2/Neu and ACTR may synergize to orchestrate mammary tumorigenesis through the dysregulation of the transcription factor ER81 and its target genes.
Mesh Terms:
Acetyltransferases, Animals, Breast Neoplasms, Carrier Proteins, Cell Cycle Proteins, Cell Line, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Glutathione Transferase, HeLa Cells, Histone Acetyltransferases, Humans, Luciferases, Models, Biological, Nuclear Proteins, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Nucleocytoplasmic Transport Proteins, Plasmids, Precipitin Tests, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, RNA, Receptor, erbB-2, Receptors, Retinoic Acid, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, p300-CBP Transcription Factors
Acetyltransferases, Animals, Breast Neoplasms, Carrier Proteins, Cell Cycle Proteins, Cell Line, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Glutathione Transferase, HeLa Cells, Histone Acetyltransferases, Humans, Luciferases, Models, Biological, Nuclear Proteins, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Nucleocytoplasmic Transport Proteins, Plasmids, Precipitin Tests, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, RNA, Receptor, erbB-2, Receptors, Retinoic Acid, Recombinant Fusion Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Apr. 09, 2004
PubMed ID: 14747462
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