Genes Cells. 1999 Sep;4(9):541-9.

Requirement of cooperative functions of two repeated death effector domains in caspase-8 and in MC159 for induction and inhibition of apoptosis, respectively.External

Tsukumo, S. I., Yonehara, S.,
--- - Institute for Virus Research, Kyoto University, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
BACKGROUND: The death effector domain (DED), which functions as a domain for a homophilic protein interaction, plays a role in death receptor-mediated apoptosis. Two tandemly repeated DEDs in the prodomain of caspase-8 (Casp8NC-DED) and those in MC159 (viral FLIP) have been shown to positively and negatively regulate apoptosis, respectively, by binding to caspase-8 and/or Fas-associated death domain (FADD). However, characteristics of each DED in Casp8NC-DED and those in MC159 have not been well examined. RESULTS: We analysed deletion and chimera mutants of DEDs derived from Casp8NC-DED and MC159, and found that MC159 and Casp8NC-DED require the combined effects of the two repeated DEDs to exert their binding and biological activities. The carboxy-terminal DED of Casp8NC-DED (Casp8C-DED) has the potential to induce apoptosis, and the amino-terminal DED of MC159 showed a dominant inhibitory effect on apoptosis when combined with Casp8C-DED. In addition, the two repeated DEDs in Casp8NC-DED and MC159 were shown to regulate the activities of caspase differently from the caspase recruitment domain (CARD) in the prodomains of caspase-2, -9 and Apaf-1. CONCLUSIONS: Although each of the DEDs in Casp8NC-DED and MC159 has the potential to stimulate or inhibit apoptosis, the combination of the two-repeated DEDs is necessary for the DED-containing proteins to stimulate or inhibit apoptosis.
PMID: 10526240External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DED Caspase8 Link Caspase8 Yeast two-hybrid Mouse 1-202 Yeast Mouse 1-202 Yeast 10526240
DED Caspase8 Link Caspase8 Yeast two-hybrid Mouse 1-202 Yeast Mouse 82-202 Yeast 10526240
DED Caspase8 Link FADD Yeast two-hybrid Mouse 1-202 Yeast Mouse 1-96 Yeast 10526240
(Link: click this icon to show interactions only between the two corresponding DDs)