title: Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB.
abstract: HTLV-1 Tax oncoprotein induces persistent activation of the transcription factor NF-kappaB and CREB (cAMP-response element-binding protein)/ATF. Transforming growth factor-beta-activated kinase 1 (TAK1) has been shown to play a critical role in these transcription factors. Here, we found that TAK1 was constitutively activated in Tax-positive HTLV-1-transformed T cells. Tax induced persistent overexpression of TAK1-binding protein 2 (TAB2), but not TAB3, which is essential for TAK1 activation. Surprisingly, TAK1 was not involved in the activation of NF-kappaB. On the other hand, JNK and p38 mitogen-activated protein kinases were activated by TAK1. In addition, ATF2, but not CREB, was a target for the TAK1-JNK pathway, and p38 negatively regulated TAK1 activity through TAB1 phosphorylation. These results indicate that Tax-mediated TAK1 activation is important for the activation of ATF2 rather than NF-kappaB.
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Suzuki
authors.forename: Pattama
authors.initials: P
authors.lastname: Singhirunnusorn
authors.forename: Akinori
authors.initials: A
authors.lastname: Mori
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D051698:Activating Transcription Factor 2; D048868:Adaptor Proteins, Signal Transducing; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C497105:ATF2 protein, human; C115163:CREB1 protein, human; C410585:TAB2 protein, human