HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element.
Human T-cell leukemia virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia. The 3' end of HTLV-I proviral DNA encodes the synthesis of two regulatory proteins, tax and rex. The 40-kDa tax protein is a nuclear protein which positively stimulates transcription from the U3 region of the viral long terminal repeat sequence. Three 21-base pair sequences in the U3 region have been found to serve as the cis-element for tax-mediated trans-activation. We now report that the tax protein can trans-activate HTLV-I LTR in the absence of de novo cellular protein synthesis. Saturated mutagenesis of the 21-base pair repeat sequence showed that specific mutations clustered in sequences homologous to the cAMP responsive element (TGACGTCA) abolish trans-activation by tax. Furthermore, although the TGACGTCN element is nearly palindromic, the mutations that abolish trans-activation are localized exclusively in the 5' 6 bases, suggesting the orientation of this element may play a role in transcription. That the purified tax protein does not bind the 21-base pair repeats or nonspecific DNA lends further support to the notion that tax protein does not directly interact with the 21-base pair repeats to activate transcription. Instead, tax most likely acts via cellular transcriptional factor(s) to bring about trans-activation.
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Department of Biochemistry, University of Nebraska Medical Center, College of Medicine, Omaha 68105.
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D001483:Base Sequence; D005786:Gene Expression Regulation; D005796:Genes; D005814:Genes, Viral; D006367:HeLa Cells / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger