Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 85K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, S. Y. Articles by Choi, Y. Search for Related Content PubMed PubMed Citation Articles by Lee, S. Y. Articles by Choi, Y. Social Bookmarking                            What's this?

Brief Definitive Reports

Stimulus-dependent Synergism of the Antiapoptotic Tumor Necrosis Factor Receptor–associated Factor 2 (TRAF2) and Nuclear Factor B Pathways

Soo Young Lee^*, David R. Kaufman, Ana L. Mora^||, Angela Santana, Mark Boothby^||,¶, and Yongwon Choi^,

From the ^* Department of Pathology, Hallym Medical School, Choonchun, Kangwon-do, 200-702, Korea; the Howard Hughes Medical Institute and The Rockefeller University, New York 10021; and the ^|| Department of Microbiology and Immunology and the ^¶ Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic signaling pathways. Thus, although TNF can cause apoptosis and may prove useful in the treatment of malignancies, most cells are resistant to TNF-induced cell death unless de novo protein synthesis is inhibited. Previous studies suggested that TNF activation of the nuclear factor (NF)-B transcription factor family antagonizes the proapoptotic signals initiated by TNF-. TNF receptor–associated factor (TRAF)2 has also been shown to mediate crucial antiapoptotic signals during TNF stimulation, yet is not essential in activation of NF-B under physiologic conditions, thus raising questions about the relationship between these antiapoptotic pathways. We report here that inhibition of TRAF2 and NF-B function in primary cells, by coexpression of a constitutive repressor of multiple NF-B/Rel proteins (IB.DN) and a dominant negative form of TRAF2 (TRAF2.DN), synergistically enhanced TNF-induced apoptosis. The effects were stimulus dependent, such that neither inhibitory molecule affected Fas- and daunorubicin-induced apoptosis to the same degree as TNF-induced death. These findings indicate that the NF-B and TRAF2 pathways activate independent antiapoptotic mechanisms which act in concert to suppress the proapoptotic signals induced by TNF-.

Key Words: apoptosis • tumor necrosis factor receptor–associated factor 2 • nuclear factor B • tumor necrosis factor • signal transduction

M. Boothby is supported by a grant from the National Institutes of Health (AI-36997), and by a Leukemia Society of America Scholar Award. Y. Choi is an investigator of the Howard Hughes Medical Institute.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS