Murine A-myb gene encodes a transcription factor, which cooperates with Ets-2 and exhibits distinctive biochemical and biological activities from c-myb.
The myb gene family consists of three members, named A-, B-, and c-myb, which encode nuclear proteins that bind to DNA and function as regulators of transcription. Our results show that murine A-myb is a poor transactivator of transcription compared with murine c-myb. Deletion of the COOH-terminal domain of A-Myb, or co-expression with Ets-2 resulted in increased transactivation potential. While ectopic overexpression of c-myb in 32Dcl3 cells results in a block to the ability of these cells to undergo terminal differentiation resulting in indefinite growth in granulocyte-colony-stimulating factor (G-CSF), similar overexpression of A-myb results in growth arrest and concomitant terminal differentiation of 32D cells into granulocytes. Co-expression of A-myb and ets-2 in these cells results in the restoration of the proliferative activity of the cells in G-CSF, but fails to induce a block to G-CSF-induced terminal differentiation. However, overexpression of the COOH-terminal deletion mutant of A-myb results in a block to G-CSF-induced differentiation of 32D cells, suggesting that the distinctive biological phenotypes produced by A-myb and c-myb genes are mediated by their COOH-terminal domains.
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Reddy
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D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D046911:Macromolecular Substances; D051379:Mice; D011401:Promoter Regions, Genetic; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494070:Ets2 protein, mouse; D046911:Macromolecular Substances; C490283:Mybl1 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor