Functional antagonism between members of the myb family: B-myb inhibits v-myb-induced gene activation.

Abstract

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.

Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

“…The chicken c-Myb expression vector was obtained by isolating the coding region of full-length c-Myb as a NcoI (partial)/XbaI fragment from pCM100 plasmid (Foos et al, 1992) and inserting it together with an oligonucleotide adapter (GAATTCACCATGG) between the EcoRI and XbaI sites of pCDNA4 (Invitrogen). pCDNA4-chcmyb-DBgl, pCDNA4-chcmyb-DSal and pCDNA4-chcmyb-DNae are derivatives encoding C-terminally truncated proteins containing c-myb amino acids 1-497, 1-303 and 1-236, respectively.…”

HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300

“…The c-Myb promoter can be activated through Ets-like and CMAT sites (Sullivan et al, 1997;Phan et al, 1996) or by c-Jun, JunD (Nicolaides et al, 1992). The Wilms' tumor suppressor WT-1, B-Myb and c-Myb proteins have been identi®ed as repressors of the c-Myb promoter activity (McCann et al, 1995;Foos et al, 1992;Nomura et al, 1993). A blockade to transcription elongation has been identi®ed within the ®rst intron of the mouse c-Myb locus (Bender et al, 1987;Watson, 1988), and a correlation between proteins binding to the intron 1 pause site and c-Myb mRNA levels has been reported (Reddy and Reddy, 1989;Castron et al, 1992).…”

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

“…DNA-binding is mediated through a comparatively large aminoterminal domain (Howe et al, 1990;Oehler et al, 1990) which demonstrates a high degree of conservation within this protein family. All three members of the Myb protein family have been reported to activate transcription from responsive promoters (Nishina et al, 1989;Weston and Bishop, 1989;Mizuguchi et al, 1990;Foos et al, 1994;Golay et al, 1994;Ma and Calabretta, 1994;Takahashi et al, 1995), however, there are distinct di erences in their transcription regulatory properties, particularly between c-Myb and B-Myb. Transactivation by c-Myb requires only the DNA binding domain and a weakly acidic region (amino acids 275 ± 325) which is conserved in A-Myb but not in B-Myb (Sakura et al, 1989;Weston and Bishop, 1989).…”

“…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).…”

“…Moreover, B-Myb has been demonstrated to repress type I collagen gene expression in smooth muscle cells (Marhamati and Sonensheim, 1996). In light of such ®ndings and the fact that B-Myb lacks the activation domain conserved between c-Myb and A-Myb, it has been suggested that B-Myb may be an inhibitory member of the Myb family (Foos et al, 1992). Other studies have shown, however, that B-Myb is a transactivator in monkey CV1 and human HeLa cell lines (Mizuguchi et al, 1990;Nakagoshi et al, 1992;Tashiro et al, 1995).…”