HTLV-1 Tax-mediated TAK1 activation involves TAB2 adapter protein.
Human T cell leukemia virus type 1 (HTLV-1) Tax is an oncoprotein that plays a crucial role in the proliferation and transformation of HTLV-1-infected T lymphocytes. It has recently been reported that Tax activates a MAPKKK family, TAK1. However, the molecular mechanism of Tax-mediated TAK1 activation is not well understood. In this report, we investigated the role of TAK1-binding protein 2 (TAB2) in Tax-mediated TAK1 activation. We found that TAB2 physically interacts with Tax and augments Tax-induced NF-kappaB activity. Tax and TAB2 cooperatively activate TAK1 when they are coexpressed. Furthermore, TAK1 activation by Tax requires TAB2 binding as well as ubiquitination of Tax. We also found that the overexpression of TRAF2, 5, or 6 strongly induces Tax ubiquitination. These results suggest that TAB2 may be critically involved in Tax-mediated activation of TAK1 and that NF-kappaB-activating TRAF family proteins are potential cellular E3 ubiquitin ligases toward Tax.
Yu
Qingsheng
Q
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Minoda
Yasumasa
Y
Yoshida
Ryoko
R
Yoshida
Hideyuki
H
Iha
Hidekatsu
H
Kobayashi
Takashi
T
Yoshimura
Akihiko
A
Takaesu
Giichi
G
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D016356:Gene Products, tax; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D044767:Ubiquitin-Protein Ligases; D000099151:MAP Kinase Kinase Kinase 7; C410585:TAB2 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1