HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination

Biochem Biophys Res Commun. 2007 May 25;357(1):225-30. doi: 10.1016/j.bbrc.2007.03.125. Epub 2007 Mar 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • I-kappa B Kinase / metabolism*
  • Jurkat Cells
  • Lysine / chemistry
  • Lysine / metabolism*
  • NF-kappa B / metabolism*
  • Signal Transduction / physiology*
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*


  • IKBKG protein, human
  • NF-kappa B
  • Ubiquitin
  • I-kappa B Kinase
  • Lysine