Tumorigenic N-terminal deletions of c-Myb modulate DNA binding, transactivation, and cooperativity with C/EBP

• Published in: Oncogene Vol. 20; no. 50; pp. 7420 - 7424
• Main Authors: OELGESCHLÄGER, Michael, KOWENZ-LEUTZ, Elisabeth, SCHREEK, Sabine, LEUTZ, Achim, LÜSCHER, Bernhard
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.11.2001; Nature Publishing Group
• Subjects: Acetyltransferases; Amino acids; Animals; Binding sites; Biological and medical sciences; c-Myb protein; C/EBP^b protein; CCAAT-Enhancer-Binding Protein-beta - metabolism; CCAAT/enhancer-binding protein; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cercopithecus aethiops; Chemical properties; Chickens; Chromatin; COS Cells; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Genes, myb; Genes, Reporter; Humans; Insertion; Kinases; Leukemia; Luciferases - biosynthesis; Luciferases - genetics; Macromolecular Substances; Mice; mim-1 gene; Molecular and cellular biology; Mutants; MYB gene; MYB protein; N-Terminus; Promoter Regions, Genetic; Protein Binding; Proteins; Proteins - genetics; Proto-Oncogene Proteins c-myb - chemistry; Proto-Oncogene Proteins c-myb - metabolism; Recombinant Fusion Proteins - biosynthesis; Sequence Deletion; Transcription activation; Transcription Factors - metabolism; Transcriptional Activation; Tumors; Germany; Chromosomal aberration; Binding; DNA; C-Onc gene; Modulation; Deletion; Abnormal chromosome; Tumorigenicity
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204922

Oncogenic activation of c-myb by retroviral insertion has been implicated in tumor formation in chicken and mice. These genetic alterations result in deregulated expression of the c-myb gene and frequently in N-terminal truncation of the c-Myb protein. We demonstrate that truncation of the c-Myb N-terminus affects DNA binding and reporter activation. However, all three mutants, Myb Delta N20, Myb Delta N47 and Myb Delta N71 cooperated with C/EBP beta in reporter assays. In contrast to Myb Delta N20 and Myb Delta N47, however, the Myb Delta N71 mutant failed to activate the chromatin embedded endogenous mim-1 gene together with C/EBP beta. This suggests that an N-terminal region (amino acids 47-71) within repeat 1 (R1) of the murine c-Myb DNA binding domain affects activation of chromosomal target genes in collaboration with C/EBP beta.