TAX PROTEIN OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I BINDS TO THE ANKYRIN MOTIFS OF INHIBITORY FACTOR KAPPA-B AND INDUCES NUCLEAR TRANSLOCATION OF TRANSCRIPTION FACTOR NF-KAPPA-B PROTEINS FOR TRANSCRIPTIONAL ACTIVATION

Human T-cell leukemia virus type I causes adult T-cell leukemia and tr opical spastic paraparesis, and its regulator protein Tax has been imp licated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through sp ecific enhancers: the 21-bp enhancer of human T-cell leukemia virus ty pe I, the nuclear factor kappa B (NF-kappa B)-binding site of the inte rleukin 2 receptor alpha gene, and the serum-responsive element of c-f os. Tax binds to enhancer-binding proteins including cAMP-responsive e lement-binding protein, cAMP-responsive element modulator, transcripti on factor NF-kappa B p50 and p67(SRF), and associates with each enhanc er DNA indirectly. In addition to this mechanism, we report here that Tax binds to inhibitory factor kappa B gamma (I-kappa B) gamma, which forms a complex with NF-kappa B protein heterodimer p50-p65 or homodim er p50-p50 and retains them in the cytoplasm. Tax binding to I-kappa B gamma induces nuclear translocation of NF-kappa B p65. In association with this nuclear translocation of p65, transcription directed by the kappa B enhancer is strongly activated. Tax binds to the ankyrin moti fs of I-kappa B gamma, suggesting its possible interaction with many o ther proteins carrying ankyrin moths contributing to various regulator y processes. This is a different mechanism of transcriptional activati on by the oncoprotein Tax and seems to be independent from the trans-a ctivation through indirect binding to enhancer DNAs.