Functional antagonism between members of the myb family: B-myb inhibits v-myb-induced gene activation.
The oncogene v-myb and its cellular progenitor c-myb encode nuclear, DNA binding phosphoproteins that control the expression of certain target genes in immature hematopoietic cells. Here, we report the isolation of a myb-related chicken gene, chicken B-myb. We show that expression of B-myb, unlike that of c-myb, is not restricted to hematopoietic cells, suggesting that B-myb functions in a broader spectrum of cell types than c-myb. We have identified the authentic chicken B-myb protein as a nuclear protein of approximately 110 kDa. We show that the B-myb protein specifically recognizes v-myb binding sites in vitro and that binding is mediated by an N-terminally located DNA binding domain. Although B-myb protein recognizes myb binding sites, B-myb fails to transactivate several myb-responsive gene constructs as well as the endogenous myb-responsive gene mim-1. Instead, we find that B-myb represses v-myb- and c-myb-mediated activation of the mim-1 gene, most likely by competing with other myb proteins for binding sites. Our results raise the possibility that B-myb is an inhibitory member of the myb family.
Foos
G
G
Hans-Spemann-Laboratory, Max-Planck-Institute for Immunobiology, Frieburg, Germany.
Grimm
S
S
Klempnauer
K H
KH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D018797:Cell Cycle Proteins; D002460:Cell Line; D002645:Chickens; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA