Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAILR2) and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is a
cell surface receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integra ...
of the
TNF-receptor
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth ...
superfamily that binds
TRAIL
A trail, also known as a path or track, is an unpaved lane or a small paved road (though it can also be a route along a navigable waterways) generally not intended for usage by motorized vehicles, usually passing through a natural area. Ho ...
and mediates
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
.
Function
The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces apoptosis signal. Mice have a homologous gene, tnfrsf10b, that has been essential in the elucidation of the function of this gene in humans. Studies with FADD-deficient mice suggested that FADD, a
death domain
The death domain (DD) is a protein interaction module composed of a bundle of six alpha helix, alpha-helices. DD is a subclass of protein structural motif , motif known as the death fold and is related in sequence and structure to the death effecto ...
containing
adaptor protein, is required for the apoptosis mediated by this protein.
Interactions
DR5 has been shown to
interact with:
*
Caspase 8
Caspase-8 is a caspase protein, encoded by the ''CASP8'' gene. It most likely acts upon caspase-3.
''CASP8'' orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present ...
,
[
* ]Caspase 10
Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.
This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution ...
,FADD
FAS-associated death domain protein, also called MORT1, is encoded by the ''FADD'' gene on the 11q13.3 region of chromosome 11 in humans.
FADD is an Signal transducing adaptor protein, adaptor protein that bridges members of the Tumor necrosi ...
,TRAIL
A trail, also known as a path or track, is an unpaved lane or a small paved road (though it can also be a route along a navigable waterways) generally not intended for usage by motorized vehicles, usually passing through a natural area. Ho ...
.
Cancer therapy
Monoclonal antibodies targeting DR5 have been developed and are currently under clinical trials for patients suffer from a variety of cancer types, see Tigatuzumab (CS-1008).
Luminescent iridium complex-peptide hybrids, serving as TRAIL mimics, have been designed, which target the death receptors DR4 and DR5 on cancer cells and induce their apoptosis.
See also
* Cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
* Tumor necrosis factor receptor
* Tigatuzumab
References
Further reading
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External links
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{{Cytokine receptor modulators
Clusters of differentiation
TNF receptor family