Tandem DEDs and CARDs suggest novel mechanisms of signaling complex assembly.
Apoptosis is an important process to maintain cellular homeostasis. Deregulated apoptosis has linked to a number of diseases, such as inflammatory diseases, neurodegenerative disorder, and cancers. A major signaling complex in the death receptor signaling pathway leading to apoptosis is death-induced signaling complex (DISC), which is regulated mainly by death effector domain (DED)-containing proteins. There are seven DED-containing proteins in human, including FADD, c-FLIP, caspase-8, caspase-10, DEDD, DEDD2, and PEA-15. The main players in DISC formation employ tandem DEDs for regulating signaling complex formation. The regulatory mechanism of signaling complex formation is important and yet remains unclear. Interestingly, three caspase recruitment domain (CARD)-containing members, which belong to the same DD superfamily as DED-containing proteins, also contains similar tandem CARDs. Recent structural studies have shown that tandem CARDs are essential for the formation of a helical signaling complex. This review summarizes recent structural studies on DED-containing proteins and especially discusses the studies on tandem DEDs and tandem CARDs, which suggest new mechanisms of signaling complex assembly.
Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, gracelo@mail.ncku.edu.tw.
Yu-Chih
YC
Lo
Su-Chang
SC
Lin
Chao-Yu
CY
Yang
Jung-Yu
JY
Tung
D017209:Apoptosis; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry / Q000502:physiology*; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000502:physiology; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D015398:Signal Transduction; D040681:Structural Homology, Protein
D053468:CARD Signaling Adaptor Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D046912:Multiprotein Complexes