ABSTRACT
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.
Subject(s)
Chickens/genetics , Genes, myb , Promoter Regions, Genetic , Proteins/genetics , RNA-Binding Proteins , Animals , Base Sequence , Binding Sites , Bone Marrow Cells/metabolism , Cell Line, Transformed , Coturnix , DNA, Complementary/chemistry , Gene Expression Regulation , Genes, Reporter , Genomic Library , Molecular Sequence Data , TransfectionABSTRACT
The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the ability of avian myeloblastosis virus (AMV) to transform myelomonocytic cells. v-Myb is thought to disrupt the differentiation of myelomonocytic cells by affecting the expression of specific target genes. To identify such genes we have analysed the gene expression in a myelomonocytic chicken cell line that carries an estrogen inducible version of v-Myb by differential display. Here we describe the identification of the chicken homolog of the mouse Pdcd4 gene as a novel v-Myb target gene. Pdcd4 is also known as MA-3, TIS and H731 and has recently been shown to suppress the transformation of epidermal cells by tumor promoters. Our results provide the first evidence that v-Myb directly regulates the expression of a potential tumor suppressor gene.
Subject(s)
Chickens/genetics , Oncogene Proteins v-myb/metabolism , Proteins/genetics , Proteins/metabolism , RNA-Binding Proteins , Alpharetrovirus/genetics , Amino Acid Sequence , Animals , Apoptosis/drug effects , Apoptosis/genetics , Apoptosis/radiation effects , Avian Myeloblastosis Virus/genetics , Base Sequence , Cell Nucleus/metabolism , Cells, Cultured , Cytarabine/pharmacology , Gene Expression Regulation , Molecular Sequence Data , Myeloid Cells/physiology , Myeloid Cells/radiation effects , Myeloid Cells/virology , Oncogene Proteins v-myb/genetics , Sequence Homology, Amino Acid , Thymus Gland/metabolism , Ultraviolet RaysABSTRACT
The complete nucleotide sequence of RNA-2 of a fungally-transmitted UK isolate of barley mild mosaic bymovirus (BaMMV isolate UK-F) was determined and compared with other published sequences, particularly UK-M, an isolate derived from the same source but which has been mechanically passaged for several years, has a deletion of about 1 kb and cannot be fungally transmitted. From an alignment of the BaMMV RNA-2 encoded protein with that for barley yellow mosaic bymovirus (BaYMV), several regions of consistent homology were identified and extensive searches made for similarities with the proteins of other fungally-transmitted viruses, especially amongst the furovirus capsid readthrough proteins which seem especially prone to deletion and which have already been implicated in fungus transmission. The amino acid combinations ER (glutamic acid-arginine) or QR (glutamine-arginine) were found consistently in all of the viruses. They occurred in positions predicted to be on the outside of the protein, and therefore available for interaction with the fungus vector, and were also within the regions prone to spontaneous deletion. In view of the lack of other structural or sequence homologies, it is suggested that these motifs are strong candidates for involvement in fungus transmission.
Subject(s)
Potyvirus/genetics , Viral Proteins/genetics , Amino Acid Sequence , Base Sequence , Hordeum/virology , Molecular Sequence Data , Myxomycetes/virology , Plant Diseases/virology , Potyvirus/isolation & purification , RNA, Viral , Sequence Homology, Amino Acid , United KingdomABSTRACT
Barley mild mosaic virus (BaMMV) is one of the agents causing the barley yellow mosaic disease. The sequence corresponding to the 3'end of the BaMMV RNA1 of a German isolate was sequenced and the coding sequence for the 251 amino acid containing capsid protein was determined. Comparison of this sequence to other potyviral sequences and to the corresponding sequence of two Japanese isolates of BaMMV was done. The three different isolates of BaMMV show a high degree of similarity.
