TY - JOUR
T1 - TNF-induced signaling in apoptosis
AU - Rath, Pramod C.
AU - Aggarwal, Bharat B.
N1 - Funding Information:
This research was supported by The Clayton Foundation for Research. We would like to thank Walter Pagel and Becky Bertrand for a critical review of the manuscript.
PY - 1999
Y1 - 1999
N2 - Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell- death mechanisms simultaneously. Activation of NF-kB-dependent genes regulates the survival and proliferative effects pf TNF, whereas activation of caspases regulates the apoptotic effects. TNF-induced apoptosis is mediated primarily through the activation of type I receptors, the death domain of which recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however, account for the role of reactive oxygen intermediates, ceramide, phospholipases, and serine proteases which are also implicated in TNF-induced apoptosis. This cascade also does not explain how type II TNF receptors which lack the death domain, induce apoptosis. Nevertheless, this review of apoptosis signaling will be limited to those proteins that makeup the cascade.
AB - Out of the almost 17 members of the TNF superfamily, TNF is probably the most potent inducer of apoptosis. TNF activates both cell-survival and cell- death mechanisms simultaneously. Activation of NF-kB-dependent genes regulates the survival and proliferative effects pf TNF, whereas activation of caspases regulates the apoptotic effects. TNF-induced apoptosis is mediated primarily through the activation of type I receptors, the death domain of which recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however, account for the role of reactive oxygen intermediates, ceramide, phospholipases, and serine proteases which are also implicated in TNF-induced apoptosis. This cascade also does not explain how type II TNF receptors which lack the death domain, induce apoptosis. Nevertheless, this review of apoptosis signaling will be limited to those proteins that makeup the cascade.
KW - Apoptosis
KW - Signaling
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=0033451738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033451738&partnerID=8YFLogxK
U2 - 10.1023/A:1020546615229
DO - 10.1023/A:1020546615229
M3 - Review article
C2 - 10634209
AN - SCOPUS:0033451738
SN - 0271-9142
VL - 19
SP - 350
EP - 364
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 6
ER -