Foos G, Grimm S, Klempnauer K H
Hans-Spemann-Laboratory, Max-Planck-Institute for Immunobiology, Frieburg, Germany.
EMBO J. 1992 Dec;11(12):4619-29. doi: 10.1002/j.1460-2075.1992.tb05564.x.
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.
癌基因v-myb及其细胞源基因c-myb编码核内DNA结合磷蛋白，这些蛋白可控制未成熟造血细胞中某些靶基因的表达。在此，我们报告了一个与myb相关的鸡基因——鸡B-myb的分离。我们发现，与c-myb不同，B-myb的表达并不局限于造血细胞，这表明B-myb在比c-myb更广泛的细胞类型中发挥作用。我们已鉴定出真正的鸡B-myb蛋白为一种约110 kDa的核蛋白。我们表明，B-myb蛋白在体外能特异性识别v-myb结合位点，且这种结合由位于N端的DNA结合结构域介导。尽管B-myb蛋白能识别myb结合位点，但它无法激活多个myb反应性基因构建体以及内源性myb反应性基因mim-1。相反，我们发现B-myb能抑制v-myb和c-myb介导的mim-1基因激活，很可能是通过与其他myb蛋白竞争结合位点来实现的。我们的结果提示B-myb可能是myb家族的一个抑制性成员。
