The cellular proto-oncogene product Myb acts as transcriptional activator of the long terminal repeat of human T-lymphotropic virus type I.
The proto-oncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and activates transcription of several viral and cellular genes. Expression of the c-myb gene is induced in mitogen- and/or antigen-stimulated T lymphocytes, which are also the preferential target cells of human T-lymphotropic virus type I (HTLV-I) in vivo and in vitro. We report here that Myb binds to the HTLV-I long terminal repeat (LTR) in four different regions in a sequence-specific manner. Electrophoretic mobility shift assay using labeled LTR fragments as well as labeled double-stranded oligonucleotides show that there are two high-affinity and two low-affinity Myb-binding sites present in the HTLV-I LTR. DNase I footprinting analysis and oligonucleotide competition experiments indicate that this binding is sequence specific. Cotransfection experiments in HeLa cells, using a Myb expression vector and chloramphenicol acetyltransferase reporter gene linked to the HTLV-I LTR, show that Myb activates HTLV-I LTR-mediated transcription by a factor of four-to sixfold. Thus, in HTLV-I-infected T cells, Myb protein binding to the HTLV-I LTR may constitute one of the signal that regulate HTLV-I transcription in vivo.
Dasgupta
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P
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104-4268.
Reddy
C D
CD
Saikumar
P
P
Reddy
E P
EP
D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral; D003850:Deoxyribonuclease I / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D012091:Repetitive Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*
D004279:DNA, Viral; C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D003850:Deoxyribonuclease I