Mol Cell Biol. 2006 Oct;26(19):7046-55.

Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.External

Merino, D., Lalaoui, N., Morizot, A., Schneider, P., Solary, E., Micheau, O.,
--- - INSERM, U517, Univ. Bourgogne, Dijon F-21000, France.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the death-inducing signaling complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with DR5 within the DISC, where it inhibits initiator caspase activation. In addition, DcR2 prevents DR4 recruitment within the DR5 DISC. The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling.
PMID: 16980609External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD DR4 Link DR5 Co-immunoprecipitation HeLa 16980609
DD DR4 Link FADD Co-immunoprecipitation HeLa 16980609
DD DR5 Link FADD Co-immunoprecipitation HepG2 16980609
(Link: click this icon to show interactions only between the two corresponding DDs)