Kaposi's sarcoma-associated herpesvirus vFLIP and human T cell lymphotropic virus type 1 Tax oncogenic proteins activate IkappaB kinase subunit gamma by different mechanisms independent of the physiological cytokine-induced pathways

• Published in: Journal of virology Vol. 85; no. 14; pp. 7444 - 7448
• Main Authors: Shimizu, Akira, Baratchian, Mehdi, Takeuchi, Yasu, Escors, David, Macdonald, Douglas, Barrett, Tracey, Bagneris, Claire, Collins, Mary, Noursadeghi, Mahdad
• Format: Journal Article
• Language: English
• Published: United States 01.07.2011
• Subjects: Cytokines - physiology; Herpesvirus 6, Human - metabolism; Herpesvirus 6, Human - physiology; Human T-lymphotropic virus 1 - metabolism; Humans; I-kappa B Kinase - chemistry; I-kappa B Kinase - metabolism; Sarcoma, Kaposi - virology; Viral Proteins - physiology
• DOI: 10.1128/JVI.02337-10

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.