Human T-cell Lymphotropic Virus Type 1 Tax Induction of Biologically Active NF-κB Requires IκB Kinase-1-mediated Phosphorylation of RelA/p65

Activation of the NF-κB pathway by the leukemogenic TEL-Jak2 and TEL-Abl fusion proteins leads to the accumulation of antiapoptotic IAP proteins and involves IKKα

“…As a similar subcellular distribution was observed in parental Ba/F3 cells cultured in the presence of WCM, these patterns attest the dynamics of IL-3-induced NF-kB activation and illustrate the capability of the leukemogenic fusion proteins to mimic this process. Phosphorylated serine536-p65/RelA species were also detected in the three cell lines; such phosphorylation of the p65 subunit has been reported in hematopoietic cells upon cytokine or LTb induction (Hayden and Ghosh, 2004) and as the consequence of the viral protein Tax-mediated cellular transformation (O'Mahony et al, 2004). The IkB-related B-cell leukemia/lymphoma 3 (Bcl-3) was found in nuclear extracts as repeatedly reported in lymphoid cells, where it is known to participate to the induction of NF-kBtarget genes in association with p50 and p52 (Dechend et al, 1999).…”

“…In T cells for example, NF-kB induction can be triggered through a TCR-independent recruitment and activation of Vav-1/IKKa complexes (Piccolella et al, 2003). In leukemogenesis, a specific role of IKKa has emerged in regard of its implication in the transforming activities of viral proteins Luftig et al, 2004;Matta and Chaudhary, 2004;O'Mahony et al, 2004) and in transgenic model of T-cell lymphomagenesis (Bellavia et al, 2000). Regarding TEL-Jak2, we failed to obtain functional data on NIK activity in our model and could neither demonstrate phospho-tyrosine IKKa species nor physical interactions between TEL-Jak2 and the IKK complex, suggesting that activation of IKKa do not involve its direct phosphorylation by the oncogene (data not shown).…”

Knockdown of Bcl-3 Inhibits Cell Growth and Induces DNA Damage in HTLV-1-infected Cells)

“…Whereas, Bcl-3 protein was barely detected in HTLV-1-negetive cell lines Jurkat, IM9, and THP-1. Tax-induced p65 nuclear translocation acts as a major cause in the increased NF-κB activity (O'Mahony, 2004;Sun et al, 1994). In the present study, p65 nuclear translocation was observed in TaxP cell line, which continuously expresses Tax ( Figure 1C).…”

Activation of NF-κB by HTLV-I and implications for cell transformation

“…IKKa plays an important role in Tax-induced phosphorylation of RelA, although IKKb is essential for Tax-induced nuclear translocation of the canonical NF-kB (O'Mahony et al, 2004). Interestingly, IKKa also serves as a central component of Tax-stimulated noncanonical NF-kB signaling pathway, which is responsible for hyperactivation of p52-containing NFkB complexes (Xiao et al, 2001a).…”