Dominant negative Tax double mutants as molecular inhibitors for w.t. Tax gene functions.
Tax plays a key role in HTLV-1 pathogenicity, partly due to its capacity of constitutive NF-kappaB activation. Delta58Tax does not translocate to the nucleus and traps w.t. Tax molecules in the cytoplasm but still retains the cytoplasmic NF-kappaB activation ability. Therefore, it enhances the w.t. Tax activation of NF-kappaB when co-expressed at lower level than w.t. Tax. However, the double mutants Delta58Tax (M22) and Delta58Tax (148) are defective also in the cytoplasmic NF-kappaB activation. They were found as capable of blocking the w.t. Tax-induced NF-kappaB-dependent activation even when expressed at low levels. These double mutants may, therefore, be used as powerful tools for blocking w.t. Tax functions.
Egbaria
Mahmoud
M
Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Tabakin-Fix
Yulia
Y
Huleihel
Mahmoud
M
D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002472:Cell Transformation, Viral; D003593:Cytoplasm / Q000378:metabolism*; D016356:Gene Products, tax / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000821:virology; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D016328:NF-kappa B; D051996:Transcription Factor RelA; C514970:tax protein, Human T-lymphotrophic virus 1; D050882:CREB-Binding Protein; C494363:CREBBP protein, human