THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 TRANSACTIVATOR PROTEIN TAX COLOCALIZES IN UNIQUE NUCLEAR-STRUCTURES WITH NF-KAPPA-B PROTEINS

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a po tent activator of viral transcription. Tax also activates the expressi on of specific cellular genes involved in the control of T-lymphocyte growth via effects on cellular transcription factors, including member s of the NF-kappa B/cRel family. Immunocytochemistry and electron micr oscopy were used to characterize the intracellular localization of Tax and identify cellular factors which are the potential targets for its transcriptional activity. These studies indicated that Tax localizes in discrete nuclear foci in T lymphocytes transformed by HTLV-1 and in cells transduced with Tax expression vectors, The Tax-containing foci are complex nuclear structures comprising a central core in which Tax colocalizes with splicing factor Sm. In addition to splicing factors Sm and SC-35, the Tax-containing nuclear structures also contain trans criptional components, including the largest subunit of RNA polymerase II and cyclin-dependent kinase CDK8. The inclusion of the two subunit s of NF-kappa B, p50 and RelA, and the presence of the mRNA from a gen e specifically activated by Tax through NF-kappa B binding sites sugge st that these unique nuclear structures participate in Tax-mediated ac tivation of gene expression via the NF-kappa B pathway.