Kaposi's Sarcoma-Associated Herpesvirus vFLIP and Human T Cell Lymphotropic Virus Type 1 Tax Oncogenic Proteins Activate IκB Kinase Subunit γ by Different Mechanisms Independent of the Physiological Cytokine-Induced Pathways

Activation of IκB kinase subunit γ (IKKγ), a key regulator of the classical NF-κB pathway, by the vFLIP protein of Kaposi's sarcoma-associated herpesvirus (KSHV) and the Tax protein of human T cell lymphotropic virus type 1 (HTLV1) is essential for virus-associated cancer. We show that vFLIP and Tax activate this pathway by different interactions with IKKγ and independently of the ubiquitin-mediated signaling pathways induced by cytokines. Our data provide new insights into the mechanisms by which IKKγ can be activated and show that NF-κB activation by oncogenic viruses can be targeted without affecting physiologically important pathways.