Oncogene. 2004 Aug 12;23(36):6083-94.

IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC.External

Ramaswamy, M., Efimova, E. V., Martinez, O., Mulherkar, N. U., Singh, S. P., Prabhakar, B. S.,
--- - Department of Microbiology and Immunology, University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA.
Recently, we identified Insulinoma-Glucagonoma clone 20 (IG20) that can render cells more susceptible to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In addition, it can slow cell proliferation, and enhance drug- and radiation-induced cell death. TNF-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in some cancer cells and render others susceptible to cotreatment with drugs and irradiation, with little or no effect on most normal cells. In this study, we investigated the potential of IG20 to enhance TRAIL-induced apoptosis and found that it can render cells more susceptible to TRAIL treatment through enhanced activation of caspases. Further, we showed that this effect can be suppressed by caspase inhibitors, p35 and CrmA, and a dominant-negative Fas-associated death domain-containing protein (DN-FADD). Results from colocalization and immunoprecipitation studies showed that IG20 can interact with TRAIL death receptors (DR), DR4 and DR5 and increase recruitment of FADD and caspase-8 into the TRAIL death-inducing signaling complex (DISC). These results indicate that IG20 is a novel protein that can enhance TRAIL-induced apoptosis by facilitating DISC formation.
PMID: 15208670External
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 MADD Co-immunoprecipitation HEK293 Not specified Not specified Human Full length 15208670
DD DR4 Link MADD Co-immunoprecipitation HEK293 Not specified Not specified Human 628-1376 15208670
DD DR4 Link MADD Fluorescence resonance energy transfer HeLa Not specified Not specified Human Full length 15208670
DD DR5 Link MADD Co-immunoprecipitation HEK293 Not specified Not specified Human Full length 15208670
DD DR5 Link MADD Co-immunoprecipitation HEK293 Not specified Not specified Human 628-1376 15208670
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DD DR4 Link MADD Immunofluorescence staining Apoptosis (DISC) 15208670
DD DR5 Link MADD Immunofluorescence staining Apoptosis (DISC) 15208670
(Link: click this icon to show interactions only between the two corresponding DDs)