Kaposi's sarcoma-associated herpesvirus (KSHV) oncoprotein K13 bypasses TRAFs and directly interacts with the IkappaB kinase complex to selectively activate NF-kappaB without JNK activation

• Published in: The Journal of biological chemistry Vol. 282; no. 34; pp. 24858 - 24865
• Main Authors: Matta, Hittu, Mazzacurati, Lucia, Schamus, Sandra, Yang, Tianbing, Sun, Qinmiao, Chaudhary, Preet M
• Format: Journal Article
• Language: English
• Published: United States 24.08.2007
• Subjects: Amino Acid Motifs; Cell Line; Herpesvirus 8, Human - metabolism; Humans; I-kappa B Kinase - metabolism; Immunoprecipitation; MAP Kinase Kinase 4 - metabolism; Models, Molecular; NF-kappa B - metabolism; Plasmids - metabolism; Protein Conformation; RNA Interference; Signal Transduction; U937 Cells; Viral Proteins - chemistry; Viral Proteins - physiology
• ISSN: 0021-9258

Kaposi's sarcoma herpesvirus oncoprotein vFLIP K13 is a potent activator of NF-kappaB and plays a key role in viral pathogenesis. K13 contains a putative TRAF-interacting motif, which is reportedly required for its interaction with TRAF2. The K13-TRAF2 interaction is believed to be essential for the recruitment of K13 to the I-kappaB kinase (IKK) complex and for K13-induced NF-kappaB and JNK activation. In addition, TRAF3 has been reported to be required for K13-induced NF-kappaB and JNK activation. We have re-examined the role of the TRAFs in K13 signaling and report that mutations in the putative TRAF-interacting motif of K13 have no deleterious effect on its ability to interact with the IKK complex or activation of the NF-kappaB pathway. Furthermore, endogenously expressed TRAF2 and TRAF3 do not interact with K13 and play no role in K13-induced NF-kappaB activation or its interaction with the IKK complex. Finally, K13 does not activate the JNK pathway. Our results support a model in which K13 bypasses the upstream components of the tumor necrosis factor receptor signaling pathway and directly interacts with the IKK complex to selectively activate the NF-kappaB pathway without affecting the JNK pathway. Selective NF-kappaB activation by K13 might represent a novel strategy employed by the virus to promote latency.