TRAF2 is essential for JNK but not NF-κB activation and regulates lymphocyte proliferation and survival

Soo Young Lee, Amy Reichlin, Angela Santana, Karen A. Sokol, Michel C. Nussenzweig, Yongwon Choi

Research output: Contribution to journalArticlepeer-review

409 Scopus citations

Abstract

TRAF2 is believed to mediate the activation of NF-κB and JNK induced by the tumor necrosis factor receptor (TNFR) superfamily, which elicits pleiotropic responses in lymphocytes. We have investigated the physiological roles of TRAF2 in these processes by expressing a lymphocyte-specific dominant negative form of TRAF2, thereby blocking this protein's effector function. We find that the TNFR superfamily signals require TRAF2 for activation of JNK but not NF-κB. In addition, we show that TRAF2 induces NF- κB-independent anti-apoptotic pathways during TNF-induced apoptosis. Inhibition of TRAF2 leads to splenomegaly, lymphadenopathy, and an increased number of B cells. These findings indicate that TRAF2 is involved in the regulation of lymphocyte function and growth in vivo.

Original languageEnglish
Pages (from-to)703-713
Number of pages11
JournalImmunity
Volume7
Issue number5
DOIs
StatePublished - Nov 1997

Bibliographical note

Funding Information:
We thank Dr. J. MacMicking for his critical comments and help in the preparation of the manuscript and Drs. H. Hanafusa, H. S. Liou, and R. Noelle for reagents. We also thank Dr. T. Mak for sharing unpublished data. This work was supported in part by a grant from Howard Hughes Medical Institute to M. C. N. and to Y. C.; A. R. is a recipient of the National Institutes of Health Clinical Investigator Development Award.

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