Myb-binding protein 1a augments AhR-dependent gene expression.
We have studied the mechanism by which an acidic domain (amino acids 515-583) of the aromatic hydrocarbon receptor (AhR) transactivates a target gene. Studies with glutathione S-transferase fusion proteins demonstrate that the wild-type acidic domain associates in vitro with Myb-binding protein 1a, whereas a mutant domain (F542A, I569A) does not. AhR-defective cells reconstituted with an AhR containing the wild-type acidic domain exhibit normal AhR function; however, cells reconstituted with an AhR containing the mutant acidic domain do not function normally. Transient transfection of Myb-binding protein 1a into mouse hepatoma cells is associated with augmentation of AhR-dependent gene expression. Such augmentation does not occur when Myb-binding protein 1a is transfected into AhR-defective cells that have been reconstituted with an AhR that lacks the acidic domain. We infer that 1) Myb-binding protein 1a associates with AhR, thereby enhancing transactivation, and 2) the presence of AhR's acidic domain is both necessary and sufficient for Myb-binding protein 1a to increase AhR-dependent gene expression.
Jones
Letetia C
LC
Division of Hematology and Oncology, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, USA.
Okino
Steven T
ST
Gonda
Thomas J
TJ
Whitlock
James P
JP
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C110421:Mybbp1a protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D005982:Glutathione Transferase