Tax protein of HTLV-1 destabilizes the complexes of NF-kappa B and I kappa B-alpha and induces nuclear translocation of NF-kappa B for transcriptional activation.
Tax protein of HTLV-1 stimulates transcription of specific cellular genes through the NF-kappa B binding site. We previously showed that Tax binds to the ankyrin motifs of I kappa B-gamma, and dissociates the I kappa B-gamma/NF-kappa B complexes, resulting in nuclear translocation of NF-kappa B proteins. We herein report the effects of Tax on I kappa B-alpha, another member of I kappa B family proteins expressed in human T cells. Tax binds to I kappa B-alpha and partially dissociates the NF-kappa B/I kappa B-alpha complex in vitro. In Tax-expressing cells, Tax/I kappa B-alpha complex was detected only at low level, but NF-kappa B/I kappa B-alpha complex was mostly dissociated and NF-kappa B was translocated into the nucleus. Furthermore, Tax induced reduction of I kappa B-alpha protein. I kappa B-alpha protein was stabilized by NF-kappa B protein through forming NF-kappa B/I kappa B-alpha complex, but Tax expression cancelled this stabilization effect on I kappa B-alpha. These findings suggest that Tax induces dissociation of and/or inhibits the formation of NF-kappa B/I kappa B-alpha complexes, resulting in release of NF-kappa B and destabilization of I kappa B-alpha. Consistently, transcription of NF-kappa B directed gene was activated. These Tax effects counteract the negative feedback control of NF-kappa B by I kappa B-alpha and contribute to constitutive activation of NF-kappa B in Tax-transfected and HTLV-1-infected cells.
Suzuki
T
T
Department of Cellular and Molecular Biology, University of Tokyo, Japan.
Hirai
H
H
Murakami
T
T
Yoshida
M
M
D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors; D015533:Transcriptional Activation
D016356:Gene Products, tax; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D051841:Transcription Factor RelB