Human T-cell leukemia virus type I Tax protein represses gene expression through the basic helix-loop-helix family of transcription factors.
The human T-cell leukemia virus type I (HTLV-I) oncoprotein Tax is a potent activator of viral and cellular gene transcription. Tax does not bind DNA directly but utilizes cellular transcription factors to mediate activation. In this report, we examine the role of the basic helix-loop-helix (bHLH) proteins in Tax deregulation of gene expression, as these proteins play a critical role in progression through the cell cycle and have been implicated in neoplastic disease. We show that the bHLH proteins do not mediate activation, but instead mediate repression of gene expression in the presence of Tax. We further show that a consensus bHLH binding site in the promoter of the beta-polymerase gene, which encodes an enzyme involved in DNA repair, mediates the previously reported repression of beta-polymerase gene expression by Tax. Together, these results suggest that Tax may induce malignant transformation, at least in part, through bHLH-mediated repression of key cellular regulatory genes.
Uittenbogaard
M N
MN
Department of Microbiology, Colorado State University, Fort Collins 80523.
Armstrong
A P
AP
Chiaramello
A
A
Nyborg
J K
JK
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D009838:Oligodeoxyribonucleotides; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase