Evidence for NF-kappaB- and CBP-independent repression of p53's transcriptional activity by human T-cell leukemia virus type 1 Tax in mouse embryo and primary human fibroblasts.
The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein can repress the transcriptional activity of the tumor suppressor protein p53. However, it remains controversial whether Tax requires NF-kappaB factors/activity and/or p300/CBP in order to inactivate p53 function. To address this issue, we have investigated Tax's effect on p53's transcriptional activation in IkappaB-kinase-deficient mouse embryonic fibroblasts (MEFs); some of which are entirely silent for Tax-induced NF-kappaB activity. We found that, in IKKalpha-/-, IKKbeta-/-, and IKKgamma-/- MEFs, p53 activation of a prototypic responsive plasmid (pG13-luciferase) was repressed by wild-type Tax. Curiously, p53's activity in MEFs was also repressed by a p300/CBP-binding deficient Tax protein. Our results highlight the complex nature of Tax-mediated repression of p53- activity, which requires further investigation.
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Akiko
A
Miyazato
Sergey
S
Sheleg
Hidekatsu
H
Iha
Yan
Y
Li
Kuan-Teh
KT
Jeang
D000818:Animals; D050882:CREB-Binding Protein; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016356:Gene Products, tax; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse