HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination.
Human T-cell leukemia virus type 1 (HTLV-1) Tax-induced activation of nuclear factor-kappaB (NFkappaB) is thought to play a critical role in T-cell transformation and onset of adult T-cell leukemia. However, the molecular mechanism of the Tax-induced NFkappaB activation remains unknown. One of the mitogen-activated protein kinase kinase kinses (MAP3Ks) members, TAK1, plays a critical role in cytokine-induced activation of NFkappaB, which involves lysine 63-linked (K63) polyubiquitination of NEMO, a noncatalytic subunit of the IkappaB kinase complex. Here we show that Tax induces K63 polyubiquitination of NEMO. However, TAK1 is dispensable for Tax-induced NFkappaB activation, and deubiquitination of the K63 polyubiquitin chain failed to block Tax-induced NFkappaB activation. In addition, silencing of other MAP3Ks, including MEKK1, MEKK3, NIK, and TPL-2, did not affect Tax-induced NFkappaB activation. These results strongly suggest that unlike cytokine signaling, Tax-induced NFkappaB activation does not involve K63 polyubiquitination-mediated MAP3K activation.
Gohda
Jin
J
Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Irisawa
Masato
M
Tanaka
Yuetsu
Y
Sato
Shintaro
S
Ohtani
Kiyoshi
K
Fujisawa
Jun-ichi
J
Inoue
Jun-ichiro
J
D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D019169:Jurkat Cells; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
C491731:IKBKG protein, human; D016328:NF-kappa B; D025801:Ubiquitin; D051550:I-kappa B Kinase; D008239:Lysine