Cloning of novel isoforms of the human Gli2 oncogene and their activities to enhance tax-dependent transcription of the human T-cell leukemia virus type 1 genome.
The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by interaction of a viral transactivator protein, Tax, and cellular transcription factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was previously determined to enhance the transactivation by Tax protein. Here we report novel forms of the human homolog of a member of the Gli oncogene family, Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP, which was described previously. Four possible isoforms (hGli2 alpha, beta, gamma, and delta) are formed by combinations of two independent alternative splicings, and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer isoforms, alpha and beta, were abundantly expressed in various cell lines including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms with the DNA-binding domain of Gal4 activated transcription when the reporter contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB binds. This activation was observed only in the presence of Tax. The 21-bp sequence in the reporter was also essential for the activation. These results suggest that simultaneous binding of hGli2 and CREB to the respective sites in the reporter seems to be critical for Tax protein to activate transcription. Consequently, it is probable that the LTR can be regulated by two independent signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S sequences in the vicinity.
Tanimura
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Department of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Japan.
Dan
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Yoshida
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D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007536:Isomerism; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000075746:Zinc Finger Protein Gli2
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C082593:GLI2 protein, human; D016356:Gene Products, tax; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2