Transcription regulation by murine B-mybis distinct from that by c-myb

Abstract

The transcription regulatory properties of murine B-myb protein were compared to those of c-myb. Whereas c-Myb trans-activated an SV40 early promoter containing multiple copies of an upstream c-Myb DNA-binding site (MBS-1), and similarly the human c-myc promoter, B-Myb was unable to do so. Full-length B-Myb translated in vitro did not bind MBS-1; however, truncation of the B-Myb C-terminus or fusion of the B-Myb DNA-binding domain to the c-Myb C-terminus showed that it was inherently competent to interact with this motif. Further evidence from co-transfection experiments, demonstrating that B-Myb inhibited trans-activation by c-Myb, suggested that failure of B-Myb to trans-activate these promoters did not simply occur through lack of binding to MBS-1. Moreover, using GAL4/B-Myb fusions, it was found that an acidic region of B-Myb, which by comparison to c-Myb was expected to contain a transcription activation domain, actually had no inherent trans-activation activity and indeed appeared to trans-inhibit c-Myb. In contrast to the above findings, both B-Myb and c-Myb were able to weakly trans-activate the DNA polymerase alpha promoter. Results obtained here demonstrate that the activities of B-Myb and c-Myb are clearly distinct and suggest that these related proteins may have different functions in regulation of target gene expression.

B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter

“…To assess the role of the B-Myb DNA-binding domain, we deleted most of the second and the third of the so-called Myb repeats from the aminoterminus of the B-Myb protein. These two repeats represent the minimal DNA-binding domain of B-Myb (Foos et al, 1992;Watson et al, 1993;Carr et al, 1996) and a protein lacking them is unable to bind to DNA. As shown in Figure 4, co-transfection the pHSPD120Luc reporter gene with an expression vector encoding the deleted protein B-MybDDBD resulted in transactivation of the reporter gene.…”

“…Like the other myb family members the B-myb protein (B-Myb) displays a highly conserved aminoacid sequence close to its aminoterminus which functions as DNA-binding domain (Foos et al, 1992;Mizuguchi et al, 1990;Watson et al, 1993;Carr et al, 1996). BMyb lacks homology to the transactivation domain conserved between c-Myb and A-Myb and its transactivation properties are strikingly di erent from those of c-Myb and A-Myb.…”

“…BMyb lacks homology to the transactivation domain conserved between c-Myb and A-Myb and its transactivation properties are strikingly di erent from those of c-Myb and A-Myb. In contrast to c-Myb and A-Myb, B-Myb does not e ciently transactivate promoters containing myb binding sites (Foos et al, 1992(Foos et al, , 1994Watson et al, 1993;Golay et al, 1994;Trauth et al, 1994;Takahashi et al, 1995). Transactivation by B-Myb has been observed in certain cell types and has been suggested to require cell-speci®c accessory proteins (Tashiro et al, 1995).…”

Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation

“…Down regulation of c-myb levels correlates with induction of terminal di erentiation of hemopoietic cells (Ho man-Liebermann and Liebermann, 1991). Unlike the other members of the family, B-Myb expression is ubiquitous and strictly correlates with cell proliferation , being highest at the G1/S border of the cell cycle (Nomura et al, 1988;Reiss et al, 1991;Watson et al, 1993). Analysis of B-Myb mRNA levels in non-dividing tissues and in the whole mouse embryo con®rms that BMyb expression is linked to DNA synthesis (Sitsmann et al, 1996;Bouwmeester et al, 1992).…”

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

“…In mouse NIH3T3 and chicken HD11 ®broblasts, B-Myb was unable to transactivate Mybresponsive promoters, and indeed when co-expressed competitively inhibited the activity of c-Myb on these promoters (Foos et al, 1992;Watson et al, 1993). Moreover, B-Myb has been demonstrated to repress type I collagen gene expression in smooth muscle cells (Marhamati and Sonensheim, 1996).…”