Transdominant human T-cell lymphotropic virus type I TAX1 mutant that fails to localize to the nucleus.
Human T-cell lymphotropic virus type I (HTLV-I) encodes a 40-kDa nuclear transactivating phosphoprotein, TAX1. The results presented in this study demonstrate that deletion of amino acids 2 through 59 of TAX1 (delta 58 TAX1) decreased transactivation of the HTLV-I long terminal repeat 10- to 20-fold. S1 nuclease analysis revealed that the decrease in transactivation of the HTLV-I long terminal repeat was associated with a lack of RNA synthesis. In contrast to the nuclear localization of the wild-type TAX1 protein, indirect immunofluorescence analysis demonstrated that delta 58 TAX1 failed to localize to the nucleus, indicating that the TAX1 nuclear localization sequence is present in amino acids 2 through 59. Cotransfection of wild-type and mutant TAX1 DNAs resulted in the cytoplasmic accumulation of TAX1 and a 25-fold decrease in transactivation. Although several possibilities which may account for this transdominant effect exist, we favor a model in which delta 58 TAX1 interferes with the nuclear localization of wild-type TAX1 protein, perhaps by forming heterodimer complexes.
Gitlin
S D
SD
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Lindholm
P F
PF
Marriott
S J
SJ
Brady
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000382:microbiology*; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection
D004279:DNA, Viral; D016356:Gene Products, tax