Loss of TRAIL-R does not affect thymic or intestinal tumor development in p53 and adenomatous polyposis coli mutant mice (original) (raw)
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- Published: 29 October 2004
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Dear Editor,
TRAIL (TNF-Related Apoptosis-Inducing Ligand) and the TRAIL receptors were originally isolated based to their homology to tumor necrosis factor (TNF) and TNF receptor (TNFR) family members.1, 2, 3 In humans, five TRAIL receptors have been characterized. Two of these receptors, DR4 and DR5, contain an intracellular protein motif known as a death domain, which can transmit an apoptotic signal. Two additional receptors, DcR1 and DcR2, lack a functional death domain and appear to function as decoy receptors to inhibit signaling by TRAIL.4 The fifth receptor, osteoprotegerin (OPG), has been shown to bind TRAIL in vitro but has low affinity for the ligand at physiological temperatures;5 therefore, it is unclear as to whether it is a true receptor for TRAIL. In mice, one full length signaling receptor (TRAIL-R) and two decoy receptors lacking death domains have been identified.6, 7 Like Fas and TNFR, TRAIL-R induces apoptosis in a broad range of transformed cell lines in a FADD- and caspase-8-dependent manner.8, 9, 10, 11 In contrast to Fas and TNFR, most nontransformed cells are resistant to TRAIL-R-mediated death;1, 12, 13 as a result, there is considerable interest in the potential role of TRAIL as a cancer therapeutic.
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Acknowledgements
We thank Kristina Hsieh for help in mouse husbandry and genotyping and James P Allison for helpful discussions about triangular mice. This work is supported by the National Institute of Health Grant CA92000 to AW. HHY is a National Science Foundation Predoctoral Research Fellow.
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- H H Yue and G E Diehl: These authors contributed equally to this work
Authors and Affiliations
- Cancer Research Laboratory and Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720-3200, USA
H H Yue, G E Diehl & A Winoto
Authors
- H H Yue
- G E Diehl
- A Winoto
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Correspondence toA Winoto.
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Yue, H., Diehl, G. & Winoto, A. Loss of TRAIL-R does not affect thymic or intestinal tumor development in p53 and adenomatous polyposis coli mutant mice.Cell Death Differ 12, 94–97 (2005). https://doi.org/10.1038/sj.cdd.4401523
- Published: 29 October 2004
- Issue date: 01 January 2005
- DOI: https://doi.org/10.1038/sj.cdd.4401523
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