Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 275 (30): 23319-23325

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Temperature-sensitive Differential Affinity of TRAIL for Its Receptors

DR5 IS THE HIGHEST AFFINITY RECEPTOR*

Alemseged Truneh{ddagger}§, Sunita Sharma{ddagger}||, Carol Silverman||**, Sanjay Khandekar**, Manjula P. Reddy{ddagger}, Keith C. Deen{ddagger}, Megan M. Mclaughlin{ddagger}, Srinivasa M. Srinivasula§§, George P. Livi{ddagger}, Lisa A. Marshall{ddagger}, Emad S. Alnemri§§, William V. Williams, , and Michael L. Doyle¶¶

From the Departments of {ddagger}Immunology, **Protein Biochemistry, {ddagger}Comparative Genetics, and ¶¶Structural Biology and the Clinical Pharmacology Unit, SmithKline Beecham Pharmaceuticals, Pennsylvania, King of Prussia and §§Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

ABSTRACT Back to Top

Abstract: TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines which induces apoptotic cell death in a variety of tumor cell lines. It mediates its apoptotic effects through one of two receptors, DR4 and DR5, which are members of of the TNF receptor family, and whose cytoplasmic regions contain death domains. In addition, TRAIL also binds to 3 "decoy" receptors, DcR2, a receptor with a truncated death domain, DcR1, a glycosylphosphatidylinositol-anchored receptor, and OPG a secreted protein which is also known to bind to another member of the TNF family, RANKL. However, although apoptosis depends on the expression of one or both of the death domain containing receptors DR4 and/or DR5, resistance to TRAIL-induced apoptosis does not correlate with the expression of the "decoy" receptors. Previously, TRAIL has been described to bind to all its receptors with equivalent high affinities. In the present work, we show, by isothermal titration calorimetry and competitive enzyme-linked immunosorbent assay, that the rank order of affinities of TRAIL for the recombinant soluble forms of its receptors is strongly temperature dependent. Although DR4, DR5, DcR1, and OPG show similar affinities for TRAIL at 4 °C, their rank-ordered affinities are substantially different at 37 °C, with DR5 having the highest affinity (K D ≤ 2 nM) and OPG having the weakest (K D = 400 nM). Preferentially enhanced binding of TRAIL to DR5 was also observed at the cell surface. These results reveal that the rank ordering of affinities for protein-protein interactions in general can be a strong function of temperature, and indicate that sizeable, but hitherto unobserved, TRAIL affinity differences exist at physiological temperature, and should be taken into account in order to understand the complex physiological and/or pathological roles of TRAIL.


Received for publication December 28, 1999. Revision received April 11, 2000.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dominant Negative Effects of Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL) Receptor 4 on TRAIL Receptor 1 Signaling by Formation of Heteromeric Complexes.
S. Neumann, J. Hasenauer, N. Pollak, and P. Scheurich (2014)
J. Biol. Chem. 289, 16576-16587
   Abstract »    Full Text »    PDF »
Decreased Affinity of Recombinant Human Tumor Necrosis Factor-related Apoptosis-inducing Ligand (rhTRAIL) D269H/E195R to Osteoprotegerin (OPG) Overcomes TRAIL Resistance Mediated by the Bone Microenvironment.
M. C. J. Bosman, C. R. Reis, J. J. Schuringa, E. Vellenga, and W. J. Quax (2014)
J. Biol. Chem. 289, 1071-1078
   Abstract »    Full Text »    PDF »
Azadirone, a Limonoid Tetranortriterpene, Induces Death Receptors and Sensitizes Human Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) through a p53 Protein-independent Mechanism: EVIDENCE FOR THE ROLE OF THE ROS-ERK-CHOP-DEATH RECEPTOR PATHWAY.
S. C. Gupta, S. K. Francis, M. S. Nair, Y.-Y. Mo, and B. B. Aggarwal (2013)
J. Biol. Chem. 288, 32343-32356
   Abstract »    Full Text »    PDF »
Crystal Structure of Human RANKL Complexed with Its Decoy Receptor Osteoprotegerin.
X. Luan, Q. Lu, Y. Jiang, S. Zhang, Q. Wang, H. Yuan, W. Zhao, J. Wang, and X. Wang (2012)
J. Immunol. 189, 245-252
   Abstract »    Full Text »    PDF »
Kinetics in Signal Transduction Pathways Involving Promiscuous Oligomerizing Receptors Can Be Determined by Receptor Specificity: Apoptosis Induction by TRAIL.
E. Szegezdi, A. M. van der Sloot, D. Mahalingam, L. O'Leary, R. H. Cool, I. G. Munoz, G. Montoya, W. J. Quax, S. de Jong, A. Samali, et al. (2012)
Mol. Cell. Proteomics 11, M111.013730
   Abstract »    Full Text »    PDF »
Increased Bone Mass in Mice after Single Injection of Anti-receptor Activator of Nuclear Factor-{kappa}B Ligand-neutralizing Antibody: EVIDENCE FOR BONE ANABOLIC EFFECT OF PARATHYROID HORMONE IN MICE WITH FEW OSTEOCLASTS.
Y. Furuya, K. Mori, T. Ninomiya, Y. Tomimori, S. Tanaka, N. Takahashi, N. Udagawa, K. Uchida, and H. Yasuda (2011)
J. Biol. Chem. 286, 37023-37031
   Abstract »    Full Text »    PDF »
2-Methoxy-5-Amino-N-Hydroxybenzamide Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis by Regulating Death Receptor 5 and Survivin Expression.
C. Stolfi, R. Caruso, E. Franze, A. Rizzo, A. Rotondi, I. Monteleone, M. C. Fantini, F. Pallone, and G. Monteleone (2011)
Mol. Cancer Ther. 10, 1969-1981
   Abstract »    Full Text »    PDF »
Unraveling the Binding Mechanism of Trivalent Tumor Necrosis Factor Ligands and Their Receptors.
C. R. Reis, A. H. G. van Assen, W. J. Quax, and R. H. Cool (2011)
Mol. Cell. Proteomics 10, M110.002808
   Abstract »    Full Text »    PDF »
Hepatocyte Death: A Clear and Present Danger.
H. Malhi, M. E. Guicciardi, and G. J. Gores (2010)
Physiol Rev 90, 1165-1194
   Abstract »    Full Text »    PDF »
{beta}-Ionone Enhances TRAIL-Induced Apoptosis in Hepatocellular Carcinoma Cells through Sp1-Dependent Upregulation of DR5 and Downregulation of NF-{kappa}B Activity.
M. O. Kim, D. O. Moon, C. H. Kang, T. K. Kwon, Y. H. Choi, and G. Y. Kim (2010)
Mol. Cancer Ther. 9, 833-843
   Abstract »    Full Text »    PDF »
Investigation into the regulation mechanisms of TRAIL apoptosis pathway by mathematical modeling.
T. Zhang, M. Wu, Q. Chen, and Z. Sun (2010)
Acta Biochim Biophys Sin 42, 98-108
   Abstract »    Full Text »    PDF »
Apomab, a fully human agonistic antibody to DR5, exhibits potent antitumor activity against primary and metastatic breast cancer.
I. Zinonos, A. Labrinidis, M. Lee, V. Liapis, S. Hay, V. Ponomarev, P. Diamond, A. C.W. Zannettino, D. M. Findlay, and A. Evdokiou (2009)
Mol. Cancer Ther. 8, 2969-2980
   Abstract »    Full Text »    PDF »
Life and death by death receptors.
M. E. Guicciardi and G. J. Gores (2009)
FASEB J 23, 1625-1637
   Abstract »    Full Text »    PDF »
Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma.
A. Labrinidis, P. Diamond, S. Martin, S. Hay, V. Liapis, I. Zinonos, N. A. Sims, G. J. Atkins, C. Vincent, V. Ponomarev, et al. (2009)
Clin. Cancer Res. 15, 1998-2009
   Abstract »    Full Text »    PDF »
Glycosaminoglycans as Potential Regulators of Osteoprotegerin Therapeutic Activity in Osteosarcoma.
F. Lamoureux, G. Picarda, L. Garrigue-Antar, M. Baud'huin, V. Trichet, A. Vidal, E. Miot-Noirault, B. Pitard, D. Heymann, and F. Redini (2009)
Cancer Res. 69, 526-536
   Abstract »    Full Text »    PDF »
Ligand-Based Targeting of Apoptosis in Cancer: The Potential of Recombinant Human Apoptosis Ligand 2/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhApo2L/TRAIL).
A. Ashkenazi, P. Holland, and S. G. Eckhardt (2008)
J. Clin. Oncol. 26, 3621-3630
   Abstract »    Full Text »    PDF »
DR4-selective Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Variants Obtained by Structure-based Design.
V. Tur, A. M. van der Sloot, C. R. Reis, E. Szegezdi, R. H. Cool, A. Samali, L. Serrano, and W. J. Quax (2008)
J. Biol. Chem. 283, 20560-20568
   Abstract »    Full Text »    PDF »
Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation.
J. Zhou, G.-D. Lu, C.-S. Ong, C.-N. Ong, and H.-M. Shen (2008)
Mol. Cancer Ther. 7, 2170-2180
   Abstract »    Full Text »    PDF »
FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor {beta}1-Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells.
K. L. Nastiuk, K. Yoo, K. Lo, K. Su, P. Yeung, J. Kutaka, D. Danielpour, and J. J. Krolewski (2008)
Mol. Cancer Res. 6, 231-242
   Abstract »    Full Text »    PDF »
Investigating the Interaction between Osteoprotegerin and Receptor Activator of NF-{kappa}B or Tumor Necrosis Factor-related Apoptosis-inducing Ligand: EVIDENCE FOR A PIVOTAL ROLE FOR OSTEOPROTEGERIN IN REGULATING TWO DISTINCT PATHWAYS.
S. Vitovski, J. S. Phillips, J. Sayers, and P. I. Croucher (2007)
J. Biol. Chem. 282, 31601-31609
   Abstract »    Full Text »    PDF »
Regulation of the Extrinsic Apoptotic Pathway by the Extracellular Matrix Glycoprotein EMILIN2.
M. Mongiat, G. Ligresti, S. Marastoni, E. Lorenzon, R. Doliana, and A. Colombatti (2007)
Mol. Cell. Biol. 27, 7176-7187
   Abstract »    Full Text »    PDF »
Receptor-mediated Endocytosis Is Not Required for Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis.
S. L. Kohlhaas, A. Craxton, X.-M. Sun, M. J. Pinkoski, and G. M. Cohen (2007)
J. Biol. Chem. 282, 12831-12841
   Abstract »    Full Text »    PDF »
Prognostic Significance of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Its Receptors in Adjuvantly Treated Stage III Colon Cancer Patients.
C. M. van Geelen, J. L. Westra, E. G. de Vries, W. Boersma-van Ek, N. Zwart, H. Hollema, H. M. Boezen, N. H. Mulder, J. T. Plukker, S. de Jong, et al. (2006)
J. Clin. Oncol. 24, 4998-5004
   Abstract »    Full Text »    PDF »
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation.
E. M. Jung, J.-W. Park, K. S. Choi, J.-W. Park, H. I. Lee, K.-S. Lee, and T. K. Kwon (2006)
Carcinogenesis 27, 2008-2017
   Abstract »    Full Text »    PDF »
Sulforaphane Sensitizes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species-Mediated Up-regulation of DR5.
H. Kim, E. H. Kim, Y. W. Eom, W.-H. Kim, T. K. Kwon, S. J. Lee, and K. S. Choi (2006)
Cancer Res. 66, 1740-1750
   Abstract »    Full Text »    PDF »
Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor {kappa}B ligand (RANKL) in human breast tumours.
C Van Poznak, S S Cross, M Saggese, C Hudis, K S Panageas, L Norton, R E Coleman, and I Holen (2006)
J. Clin. Pathol. 59, 56-63
   Abstract »    Full Text »    PDF »
Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis.
L. Clancy, K. Mruk, K. Archer, M. Woelfel, J. Mongkolsapaya, G. Screaton, M. J. Lenardo, and F. K.-M. Chan (2005)
PNAS 102, 18099-18104
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Rheumatoid Arthritis Synovial Fibroblast Proliferation through Mitogen-activated Protein Kinases and Phosphatidylinositol 3-Kinase/Akt.
J. Morel, R. Audo, M. Hahne, and B. Combe (2005)
J. Biol. Chem. 280, 15709-15718
   Abstract »    Full Text »    PDF »
Target Cell-Restricted Apoptosis Induction of Acute Leukemic T Cells by a Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Fusion Protein with Specificity for Human CD7.
E. Bremer, D. F. Samplonius, M. Peipp, L. van Genne, B.-J. Kroesen, G. H. Fey, M. Gramatzki, L. F.M.H. de Leij, and W. Helfrich (2005)
Cancer Res. 65, 3380-3388
   Abstract »    Full Text »    PDF »
TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF.
G. Zauli, E. Rimondi, V. Nicolin, E. Melloni, C. Celeghini, and P. Secchiero (2004)
Blood 104, 2044-2050
   Abstract »    Full Text »    PDF »
The Role of Osteoprotegerin and Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Microvascular Endothelial Cell Survival.
L. B. Pritzker, M. Scatena, and C. M. Giachelli (2004)
Mol. Biol. Cell 15, 2834-2841
   Abstract »    Full Text »    PDF »
Osteoprotegerin/Osteoclastogenesis Inhibitory Factor Decreases Human Prostate Cancer Burden in Human Adult Bone Implanted into Nonobese Diabetic/Severe Combined Immunodeficient Mice.
H. Yonou, N. Kanomata, M. Goya, T. Kamijo, T. Yokose, T. Hasebe, K. Nagai, T. Hatano, Y. Ogawa, and A. Ochiai (2003)
Cancer Res. 63, 2096-2102
   Abstract »    Full Text »    PDF »
Osteoprotegerin Is a Soluble Decoy Receptor for Tumor Necrosis Factor-related Apoptosis-inducing Ligand/Apo2 Ligand and Can Function as a Paracrine Survival Factor for Human Myeloma Cells.
C. M. Shipman and P. I. Croucher (2003)
Cancer Res. 63, 912-916
   Abstract »    Full Text »    PDF »
Identification of a New Murine Tumor Necrosis Factor Receptor Locus That Contains Two Novel Murine Receptors for Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL).
P. Schneider, D. Olson, A. Tardivel, B. Browning, A. Lugovskoy, D. Gong, M. Dobles, S. Hertig, K. Hofmann, H. Van Vlijmen, et al. (2003)
J. Biol. Chem. 278, 5444-5454
   Abstract »    Full Text »    PDF »
Acceleration of Human Neutrophil Apoptosis by TRAIL.
S. A. Renshaw, J. S. Parmar, V. Singleton, S. J. Rowe, D. H. Dockrell, S. K. Dower, C. D. Bingle, E. R. Chilvers, and M. K. B. Whyte (2003)
J. Immunol. 170, 1027-1033
   Abstract »    Full Text »    PDF »
Adriamycin Sensitizes the Adriamycin-resistant 8226/Dox40 Human Multiple Myeloma Cells to Apo2L/Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated (TRAIL) Apoptosis.
A. R. Jazirehi, C.-P. Ng, X.-H. Gan, G. Schiller, and B. Bonavida (2001)
Clin. Cancer Res. 7, 3874-3883
   Abstract »    Full Text »    PDF »
Ewing's Sarcoma Family Tumors Are Sensitive to Tumor Necrosis Factor-related Apoptosis-inducing Ligand and Express Death Receptor 4 and Death Receptor 5.
N. Mitsiades, V. Poulaki, C. Mitsiades, and M. Tsokos (2001)
Cancer Res. 61, 2704-2712
   Abstract »    Full Text »
Differential Regulation of the Expression of CD95 Ligand, Receptor Activator of Nuclear Factor-{kappa}B Ligand (RANKL), TNF-Related Apoptosis-Inducing Ligand (TRAIL), and TNF-{alpha} During T Cell Activation.
R. Wang, L. Zhang, X. Zhang, J. Moreno, X. Luo, M. Tondravi, and Y. Shi (2001)
J. Immunol. 166, 1983-1990
   Abstract »    Full Text »    PDF »
Crystal Structure of TRAIL-DR5 Complex Identifies a Critical Role of the Unique Frame Insertion in Conferring Recognition Specificity.
S.-S. Cha, B.-J. Sung, Y.-A. Kim, Y.-L. Song, H.-J. Kim, S. Kim, M.-S. Lee, and B.-H. Oh (2000)
J. Biol. Chem. 275, 31171-31177
   Abstract »    Full Text »    PDF »
Crystal Structure of TRAIL-DR5 Complex Identifies a Critical Role of the Unique Frame Insertion in Conferring Recognition Specificity.
S.-S. Cha, B.-J. Sung, Y.-A. Kim, Y.-L. Song, H.-J. Kim, S. Kim, M.-S. Lee, and B.-H. Oh (2000)
J. Biol. Chem. 275, 31171-31177
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882