This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, Y.-S. Articles by Liu, Z.-g. Search for Related Content PubMed PubMed Citation Articles by Kim, Y.-S. Articles by Liu, Z.-g.

TRAF2 Plays a Key, Nonredundant Role in LIGHT-Lymphotoxin ß Receptor Signaling

Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda,¹ Basic Research Program, SAIC-Frederick, Inc., and Laboratory of Molecular Immunoregulation, NCI-Frederick, Frederick, Maryland²

Received 20 August 2004/ Returned for modification 17 September 2004/ Accepted 17 December 2004

LIGHT is a member of the tumor necrosis factor (TNF) superfamily, and its function is mediated by at least two receptors, including lymphotoxin ß receptor (LTßR) and herpes simplex virus entry mediator. However, the molecular mechanism of LIGHT signaling mediated by LTßR has not been clearly defined. In this report, we demonstrate that TRAF2 is critical for LIGHT- and LTßR-mediated activation of both the transcription factor NF-B and the mitogen-activated protein kinase JNK. In HeLa cells, LIGHT induces NF-B and JNK activation, which can be blocked by the dominant negative mutant of TRAF2. In these cells, LIGHT causes the recruitment of TRAF2, TRAF3, and IB kinase into the LTßR complex. Importantly, while both NF-B and JNK are activated by LIGHT in wild-type mouse embryonic fibroblasts, no activation of either of these two pathways is observed in TRAF2 null fibroblasts. However, LIGHT-induced NF-B and JNK activation can be restored by ectopic expression of TRAF2 in TRAF2^–/– cells. Interestingly, in contrast to TNF signaling, the activation of both NF-B and JNK by LIGHT was normal in RIP^–/– and TRAF5^–/– cells. Taken together, our data demonstrate that TRAF2, an important effector molecule of TNF signaling, plays a critical, nonredundant role in LIGHT-LTßR signaling.

This article has been cited by other articles:

• Madge, L. A., Kluger, M. S., Orange, J. S., May, M. J. (2008). Lymphotoxin-{alpha}1{beta}2 and LIGHT Induce Classical and Noncanonical NF-{kappa}B-Dependent Proinflammatory Gene Expression in Vascular Endothelial Cells. J. Immunol. 180: 3467-3477 [Abstract] [Full Text]  
• He, J. Q., Saha, S. K., Kang, J. R., Zarnegar, B., Cheng, G. (2007). Specificity of TRAF3 in Its Negative Regulation of the Noncanonical NF-{kappa}B Pathway. J. Biol. Chem. 282: 3688-3694 [Abstract] [Full Text]  
• Lukashev, M., LePage, D., Wilson, C., Bailly, V., Garber, E., Lukashin, A., Ngam-ek, A., Zeng, W., Allaire, N., Perrin, S., Xu, X., Szeliga, K., Wortham, K., Kelly, R., Bottiglio, C., Ding, J., Griffith, L., Heaney, G., Silverio, E., Yang, W., Jarpe, M., Fawell, S., Reff, M., Carmillo, A., Miatkowski, K., Amatucci, J., Crowell, T., Prentice, H., Meier, W., Violette, S. M., Mackay, F., Yang, D., Hoffman, R., Browning, J. L. (2006). Targeting the Lymphotoxin-{beta} Receptor with Agonist Antibodies as a Potential Cancer Therapy. Cancer Res. 66: 9617-9624 [Abstract] [Full Text]  
• Esparza, E. M., Lindsten, T., Stockhausen, J. M., Arch, R. H. (2006). Tumor Necrosis Factor Receptor (TNFR)-associated Factor 5 Is a Critical Intermediate of Costimulatory Signaling Pathways Triggered by Glucocorticoid-induced TNFR in T Cells. J. Biol. Chem. 281: 8559-8564 [Abstract] [Full Text]