Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Constitutive activation of NF-kappa B is essential for transformation of rat fibroblasts by the human T-cell leukemia virus type I Tax protein.

EMBO J. 1996 Feb 15;15(4):873-87. Unique Identifier : AIDSLINE MED/96181365
Yamaoka S; Inoue H; Sakurai M; Sugiyama T; Hazama M; Yamada T; Hatanaka M; Department of Viral Oncology, Institute for Virus Research, Kyoto; University, Japan.

Abstract: 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.

Keywords: Amino Acid Sequence Animal Base Sequence Cell Line *Cell Transformation, Neoplastic DNA-Binding Proteins/METABOLISM Gene Products, tax/*PHYSIOLOGY *Genes, pX Human Molecular Sequence Data NF-kappa B/*METABOLISM Oligonucleotide Probes/CHEMISTRY Point Mutation Rats Structure-Activity Relationship Support, Non-U.S. Gov't Trans-Activation (Genetics) JOURNAL ARTICLE
960930
M9690918

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