Abstract
TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon binding to its death domain-containing receptors, DR4 and DR5. Two additional TRAIL receptors, TRID/DcR1 and DcR2, lack functional death domains and function as decoy receptors for TRAIL. We have identified a fifth TRAIL receptor, namely osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homologue that inhibits osteoclastogenesis and increases bone density in vivo. OPG-Fc binds TRAIL with an affinity of 3.0 nM, which is slightly weaker than the interaction of TRID-Fc or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL.
MeSH Terms
Animals
Apoptosis/physiology
Apoptosis Regulatory Proteins
Binding, Competitive
GPI-Linked Proteins
Glycoproteins/physiology
Humans
Immunoglobulin Fc Fragments/genetics
Immunohistochemistry
Jurkat Cells
Ligands
Membrane Glycoproteins/physiology
Mice
Microscopy, Fluorescence
Oligopeptides
Osteoclasts/cytology
Osteoprotegerin
Peptides/immunology
Protein Binding/physiology
Receptors, Cytoplasmic and Nuclear
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor/classification,metabolism,physiology
Receptors, Tumor Necrosis Factor, Member 10c
Receptors, Tumor Necrosis Factor, Member 25
Recombinant Fusion Proteins/metabolism
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor Decoy Receptors
Tumor Necrosis Factor-alpha/physiology
Chemicals
Apoptosis Regulatory Proteins
GPI-Linked Proteins
Glycoproteins
Immunoglobulin Fc Fragments
Ligands
Membrane Glycoproteins
Oligopeptides
Osteoprotegerin
Peptides
Receptors, Cytoplasmic and Nuclear
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Member 10c
Receptors, Tumor Necrosis Factor, Member 25
Recombinant Fusion Proteins
TNF-Related Apoptosis-Inducing Ligand
TNFRSF10B protein, human
TNFRSF10C protein, human
TNFRSF11B protein, human
TNFRSF25 protein, human
TNFSF10 protein, human
Tnfrsf10b protein, mouse
Tnfrsf11b protein, mouse
Tnfrsf25 protein, mouse
Tnfsf10 protein, mouse
Tumor Necrosis Factor Decoy Receptors
Tumor Necrosis Factor-alpha
FLAG peptide
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Emery J G
Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA.
McDonnell P
Burke M B
Deen K C
Lyn S
Silverman C
Dul E
Appelbaum E R
Eichman C
DiPrinzio R
Dodds R A
James I E
Rosenberg M
Lee J C
Young P R