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

Abstract

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.