Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.
Human T-cell leukemia virus type I (HTLV-I) encodes a 40 kDa trans-acting protein, Tax, that regulates transcription of both the proviral and cellular genes, and can transform rat fibroblasts. To determine the functional importance of its trans-acting capacities in cell transformation, we have examined two representative pathways of transcriptional activation--HTLV-I long terminal repeat (LTR) mediated and NF-kappa B dependent--by mutational analysis of Tax. In contrast to a previous report, mutants lacking the ability to activate an NF-kappaB-dependent promoter failed to transform rat fibroblasts, whereas a mutation which abolishes the HTLV-I LTR-mediated trans-activation demonstrated a wild-type capacity for cell transformation. Stable expression of Tax competent for transformation caused enhanced DNA binding of NF-kappa B in rat fibroblasts. We also demonstrate that stable co-expression of the NFKB2 precursor, known as a member of the I kappa B proteins, with wild-type Tax blocked transformation as well as eliminated aberrant NF-kappaB activation by Tax without interference with the HTLV-I LTR-mediated trans-activation. Our results indicate that constitutive activation of NF-kappa B is essential for Tax-mediated transformation of rat fibroblasts.
Yamaoka
S
S
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Japan.
Inoue
H
H
Sakurai
M
M
Sugiyama
T
T
Hazama
M
M
Yamada
T
T
Hatanaka
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism; D016356:Gene Products, tax / Q000502:physiology*; D016355:Genes, pX; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000737:chemistry; D017354:Point Mutation; D051381:Rats; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D016328:NF-kappa B; D015345:Oligonucleotide Probes