|
|
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
J. Exp. Med.,
Volume 188, Number 7, October 5, 1998 1381-1384
B Pathways
By
¶§
From the * Department of Pathology, Hallym Medical School, Choonchun, Kangwon-do, 200-702, Korea; the 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)- 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
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-.
B;
tumor necrosis factor;
signal transduction
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
