TY - CHAP
T1 - Regulation of TRAIL-Induced Apoptosis by Ectopic Expression of Antiapoptotic Factors
AU - Aggarwal, Bharat B.
AU - Bhardwaj, Uddalak
AU - Takada, Yasunari
N1 - Funding Information:
We thank Walter Pagel for his careful review of this manuscript. This work was supported by the Clayton Foundation for Research (to BBA), Department of Defense US Army Breast Cancer Research Program grant (BC010610, to BBA), a PO1 grant (CA91844) from the National Institutes of Health on lung chemoprevention (to BBA) and a P50 Head and Neck SPORE grant from the National Institutes of Health (to BBA), and a Cancer Center Support Grant CA 16672. Dr. Aggarwal is a Ransom Horne, Jr. Distinguished Professor of Cancer Research.
PY - 2004
Y1 - 2004
N2 - The discovery of an agent that selectively kills tumor cells and not normal cells is the dream of every cancer researcher. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), first discovered in 1995, was heralded as a selective killer of tumor cells, and its potential is still thought to be high. Almost immediately, broad efforts were made to understand its activity at the molecular level. TRAIL has been shown to interact with the cell surface through five distinct receptors, named death receptor (DR) 4, DR5, decoy receptor (Dc)R1, DcR2, and osteoprotegrin. It activates nuclear factor (NF)-κB, c-Jun N-terminal kinases, and apoptosis. The apoptotic signals are mediated through Fas-associated death domain protein (FADD)-mediated recruitment of caspase-8 and caspase-3. Additionally, caspase-8 can cleave Bcl-2 homology domain 3 (BH3)-interfering domain death agonist (Bid), and the cleaved Bid then causes the release of mitochondrial cytochrome c, leading to the activation of pro-caspase-9, which can then activate pro-caspase-3. TRAIL-induced apoptosis is negatively regulated by numerous cellular factors including decoy receptors, cellular FADD-like interleukin 1 β-converting enzyme (FLICE) interacting protein (cFLIP), cellular inhibitor of apoptosis protein (cIAP), X-linked IAP (XIAP), survivin, and NF-κB. Second mitochondria-derived activator of caspases (Smac){plus 45 degree rule}direct IAP binding protein with low pI (DIABLO) mediates proapoptotic signals through inaction of IAP. How the TRAIL-induced apoptosis is downregulated by these factors is discussed in detail in this review. Whether TRAIL selectively kills tumor cells without harming normal cells is also discussed.
AB - The discovery of an agent that selectively kills tumor cells and not normal cells is the dream of every cancer researcher. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), first discovered in 1995, was heralded as a selective killer of tumor cells, and its potential is still thought to be high. Almost immediately, broad efforts were made to understand its activity at the molecular level. TRAIL has been shown to interact with the cell surface through five distinct receptors, named death receptor (DR) 4, DR5, decoy receptor (Dc)R1, DcR2, and osteoprotegrin. It activates nuclear factor (NF)-κB, c-Jun N-terminal kinases, and apoptosis. The apoptotic signals are mediated through Fas-associated death domain protein (FADD)-mediated recruitment of caspase-8 and caspase-3. Additionally, caspase-8 can cleave Bcl-2 homology domain 3 (BH3)-interfering domain death agonist (Bid), and the cleaved Bid then causes the release of mitochondrial cytochrome c, leading to the activation of pro-caspase-9, which can then activate pro-caspase-3. TRAIL-induced apoptosis is negatively regulated by numerous cellular factors including decoy receptors, cellular FADD-like interleukin 1 β-converting enzyme (FLICE) interacting protein (cFLIP), cellular inhibitor of apoptosis protein (cIAP), X-linked IAP (XIAP), survivin, and NF-κB. Second mitochondria-derived activator of caspases (Smac){plus 45 degree rule}direct IAP binding protein with low pI (DIABLO) mediates proapoptotic signals through inaction of IAP. How the TRAIL-induced apoptosis is downregulated by these factors is discussed in detail in this review. Whether TRAIL selectively kills tumor cells without harming normal cells is also discussed.
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U2 - 10.1016/S0083-6729(04)67023-3
DO - 10.1016/S0083-6729(04)67023-3
M3 - Chapter
C2 - 15110190
AN - SCOPUS:3042743700
SN - 0127098674
SN - 9780127098678
T3 - Vitamins and Hormones
SP - 453
EP - 483
BT - TRAIL (TNF-Related Apoptosis-Inducing Ligand)
PB - Academic Press Inc.
ER -