RESUMO
The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which disrupts the myelomonocytic differentiation program and transforms myelomonocytic cells in vivo and in vitro. It is thought that v-Myb exerts its biological effects by deregulating the expression of specific target genes, most of which are still unknown. c-myb, the cellular progenitor of v-myb, is expressed in all immature hematopoietic cells and is presumed to regulate the expression of genes that are essential for the development of the hematopoietic system. Recently, we have identified the chicken Pdcd4 gene as a novel v-myb target gene. Pdcd4 has originally been identified in a screen for genes upregulated in apoptotic cells and, more recently, has been implicated in tumor progression. As a myb-regulated gene Pdcd4 is of interest because unlike most other myb target genes it is expressed in a broad spectrum of hematopoietic cells. As a first step to study the regulation of Pdcd4 expression in more detail, we here report the identification and preliminary characterization of the myb-inducible promoter of the Pdcd4 gene.
Assuntos
Galinhas/genética , Genes myb , Regiões Promotoras Genéticas , Proteínas/genética , Proteínas de Ligação a RNA , Animais , Sequência de Bases , Sítios de Ligação , Células da Medula Óssea/metabolismo , Linhagem Celular Transformada , Coturnix , DNA Complementar/química , Regulação da Expressão Gênica , Genes Reporter , Biblioteca Genômica , Dados de Sequência Molecular , TransfecçãoRESUMO
Myc is a key regulator of cell growth, differentiation and apoptosis, and affects cell fate decisions by activating as well as by inhibiting the expression of cellular genes. Myc is a member of the basic region-helix-loop-helix-leucine zipper (b-HLH-Zip) class of transcription factors, which heterodimerizes with the Max protein and recognizes a consensus Myc binding motif. Stimulation of gene expression by Myc is thought to be mediated by direct binding of Myc-Max heterodimers to specific target genes. So far, only a few genes have been identified as direct binding targets of Myc, raising the possibility that Myc affects gene expression also by indirect mechanisms. In this work we present evidence that v-Myc encoded by the avian retrovirus MC29 stimulates activating transcription factor 2 (ATF2)-dependent transcription. Analysis of the effect of Myc on ATF2 shows that v-Myc prolongs the half-life of ATF2 and induces the phosphorylation of N-terminal sites of ATF2 (Thr-69 and Thr-71) which have previously been identified as the target sites of stress-activated protein kinases and implicated in the regulation of ATF2 activity. Taken together, our results suggest that v-Myc can affect gene expression indirectly by modulating the activity of ATF2.