"Abnormal activation of transcription factor NF-kB by oncoprotein of Human T cell leukemia Virus 1 (HTLV-1)"

Speaker: Prof. Jun-ichiro Inoue

Division of Cellular and Molecular Biology, Department of Cancer Biology

Institute of Medical Science, University of Tokyo

Title: Abnormal activation of transcription factor NF-kB by oncoprotein of Human T cell leukemia Virus 1 (HTLV-1)

Abstract: Activation of NF-kB by human T cell leukemia virus type 1 Tax is thought to be crucial in T cell transformation and the onset of adult T cell leukemia. Tax constitutively activates NF-kB through activation of the IkB kinase (IKK) complex, which is only transiently activated in response to physiological stimulation in a polyubiquitination-dependent manner. Although polyubiquitination of Tax was reported to be required for IKK activation, most studies have been performed using intact cells, in which secondary NF-kB activation can be induced by various cytokines that are secreted due to Tax-mediated primary NF-kB activation. Therefore, a cell-free assay system, in which IKK can be activated by adding highly purified recombinant Tax to cytosolic extract, was used to analyze Tax-induced IKK activation. In contrast to the cytosolic extract, the purified IKK complex was not activated by Tax, whereas it was efficiently activated by MEKK1, which does not require polyubiquitination to activate IKK. Critical roles of various polyubiquitin chains in the Tax-induced NF-kB activation will be discussed.

Host:  Tadashi Yamamoto, Cell Signal Unit