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Updated: Apr 20, 2026

Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
Tandem DEDs and CARDs suggest novel mechanisms of signaling complex assembly
Yu-Chih Lo1, Su-Chang Lin, Chao-Yu Yang
1Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, gracelo@mail.ncku.edu.tw.
Abstract:
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.
Insights
Cellular homeostasis relies on apoptosis. This review explores how tandem death effector domains (DEDs) and caspase recruitment domains (CARDs) in signaling proteins regulate apoptosis, suggesting new assembly mechanisms.
Area of Science:
- Molecular Biology
- Cell Biology
- Structural Biology
Background:
- Apoptosis is crucial for cellular homeostasis, and its dysregulation is implicated in diseases like cancer and inflammatory disorders.
- The death-induced signaling complex (DISC) is a key regulator of apoptosis, primarily controlled by death effector domain (DED)-containing proteins.
- Seven DED-containing proteins exist in humans, including FADD, c-FLIP, caspase-8, and caspase-10, which utilize tandem DEDs for signaling complex formation.
Purpose of the Study:
- To review recent structural studies on DED-containing proteins.
- To elucidate the mechanisms of signaling complex assembly involving tandem DEDs and tandem CARDs.
- To highlight potential new mechanisms for regulating apoptosis.
Main Methods:
- Literature review of recent structural studies.
- Analysis of protein structures focusing on DED and CARD domains.
- Discussion of signaling complex formation and assembly mechanisms.
Main Results:
- Tandem DEDs are critical for DISC formation and regulation.
- Caspase recruitment domain (CARD)-containing proteins share structural similarities with DED proteins.
- Recent structural data reveal tandem CARDs are essential for helical signaling complex formation.
Conclusions:
- Structural insights into DED and CARD domains provide a basis for understanding signaling complex assembly.
- Tandem DEDs and CARDs suggest novel mechanisms for regulating apoptosis.
- Further research into these domains can illuminate pathways involved in disease.
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