IkappaB-zeta, a regulator of NF-kappaB, contributes to the pathogenesis of ATL

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of the Ryukyus
• Principal Investigator: MORI Naoki 琉球大学, 医学(系)研究科(研究院), 教授 (10220013)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: HTLV-1 / 成人T細胞白血病 / NF-κB / IκB-ζ / Tax / LMP-1 / CD30 / EBウイルス

Outline of Final Research Achievements

NF-κB activation is important in the transformation and development process in ATL, Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL). HTLV-1 Tax, EB virus (EBV) LMP-1 and ligand-independent signaling by over- expressed CD30 are known to cause permanent activation of NF-κB in lymphomas. However, hyper-activation of NF-κB triggers cellular senescence and apoptosis. IκB-ζ, an inducible regulator of NF-κB, was constitutively expressed in the nuclei of ATL, BL and HL cells. Expression of Tax, LMP-1 and CD30 trans-activated the IκB-ζ gene through NIK/IKK/NF-κB pathway. IκB-ζ induced the expression of NF-κB- and IFN-regulatory genes in T cells. IκB-ζ enhanced Tax-induced transactivation of Bcl-3 and iNOS. Interestingly, IκB-ζ inhibited NF-κB activation by Tax, LMP-1 and CD30, and HTLV-1 transcription. NF-κB-induced IκB-ζ modulates NF-κB activation, resulting in a fine balance that ultimately endows a net evolutionary benefit to the survival of lymphoma cells.

Free Research Field

血液腫瘍学