Subcellular redistribution of HTLV-1 Tax protein by NF-kappa B/Rel transcription factors.
The viral oncogene Tax derived from human T cell leukemia virus type I (HTLV-I) is a positive transcriptional activator of HTLV-1 gene expression. Tax is also able to indirectly stimulate transcription of several growth regulatory genes by an indirect mechanism via association with host transcription factors. One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B/Rel family transcription factors, pleiotropic regulators of immunoregulatory, cytokine, and viral gene expression. Recent studies demonstrated that specific subunits of NF-kappa B (NFKB2(p 100) and c-Rel) were overexpressed in HTLV-I-infected and Tax-expressing cells. Furthermore, Tax physically associated with NFKB2(p 100). Monospecific antibodies directed against individual NF-kappa B subunits were generated and used to investigate the consequences of the interactions between Tax and NF-kappa B in a cotransfection-immunofluorescence assay. These studies demonstrate: (1) distinct compartmentalization of NF-kappa B precursors and products, (2) differential induction of the endogenous I kappa B alpha protein by transfected NF-kappa B subunits, (3) subcellular relocalization of Tax to the cytoplasm or nucleus depending on the coexpressed NF-kappa B subunit, and (4) Tax interaction with the Rel homology domain region of NFKB2. These studies indicate that the transcription modulatory influence of HTLV-I Tax may be significantly influenced by cytoplasmic-nuclear partitioning associated with the NF-kappa B proteins.
Pepin
N
N
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
Roulston
A
A
Lacoste
J
J
Lin
R
R
Hiscott
J
J
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D016356:Gene Products, tax / Q000032:analysis*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry*; D007106:Immune Sera / Q000276:immunology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011817:Rabbits
D016356:Gene Products, tax; D007106:Immune Sera; D016328:NF-kappa B; D004247:DNA