Activation of NF-kappa B by the Tax protein of HTLV-1.
The Tax protein, encoded by the human T cell leukemia virus HTLV-1, is responsible for transcriptional activation of the viral genome through conserved 21bp repeats located in its promoter. Tax also activates the transcription of cellular genes such as interleukin 2, interleukin 2 receptor (IL2R), GM-CSF, vimentin, c-fos, c-jun as well as the major histocompatibility complex class I genes. Tax does not bind DNA directly, but seems to activate transcription indirectly by enhancing the activity of the transcription factors that recognize responsive elements located in the promoters of the Tax-responsive genes, or by forming ternary complexes with these factors and DNA. One class of target sites for Tax are the kappa B sequences which are bound by members of the rel/NF-kappa B family. It has been previously shown that Tax is able to induce nuclear translocation of NF-kappa B. The activity of the NF-kappa B transcription factor is normally controlled through cytoplasmic retention by either of two types of molecules: the inhibitor I kappa B alpha/MAD3 or the p105 and p100 precursors of the p50 and p52 DNA-binding subunits. Treatment of cells with classical NF-kappa B inducers like TNF, IL-1, PMA or LPS results in MAD-3 degradation followed by nuclear translocation of NF-kappa B. On the other hand, the mechanisms involved in the dissociation of the cytoplasmic p105/p100-containing complexes are largely unknown. We demonstrate here that Tax can induce translocation of members of the NF-kappa B family retained in the cytoplasm through interaction with either p105 or p100. On the other hand Tax induces no apparent degradation of MAD-3. These results suggest that Tax activates NF-kappa B essentially through the p105/p100-retention pathway.
Munoz
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E
Unité de Biologie Moléculaire de l'Expression Génique, Institut Pasteur, Paris, France.
Israël
A
A
D000818:Animals; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D015533:Transcriptional Activation / Q000276:immunology*
D016356:Gene Products, tax; D016328:NF-kappa B