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

Oncogenic activation of c-myb by retroviral insertion has been implicated f it tumor formation in chicken and mice. These genetic alterations result in deregulated expression of the: c-myb gene and frequently in, N-terminal tr uncation 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, embed ded 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 co llaboration with C/EBP beta.