The versatile roles of CARDs in regulating apoptosis, inflammation, and NF-κB signaling

Area of Science:

• Cellular Biology
• Molecular Biology
• Immunology

Background:

• The CARD (caspase activation and recruitment domains) subfamily is the second largest in the DD superfamily.
• CARD-containing proteins regulate key signaling pathways including NF-kB activation, apoptosis, and inflammation.
• These proteins are essential for assembling signaling complexes like the apoptosome and inflammasome via CARD-CARD interactions.

Purpose of the Study:

• To update the classification of CARD-containing proteins using diverse schemes.
• To elucidate the structural and functional diversity of CARD-containing proteins.
• To provide an overview of CARD protein roles in signaling and therapeutic targets.

Main Methods:

• Review of existing literature and structural studies on CARD proteins.
• Classification of CARD-containing proteins based on domain structures, functions, and associated signaling complexes.
• Categorization of CARD-containing complexes into homodimeric, heterodimeric, oligomeric, filamentous, and CARD-ubiquitin complexes.

Main Results:

• A comprehensive classification of 33 human CARD-containing proteins is presented.
• Recent structural studies on CARDs and their complexes are summarized.
• CARD-containing complexes are categorized, highlighting their diverse assembly mechanisms.

Conclusions:

• Understanding CARD protein classification aids in comprehending their structural and functional diversity.
• CARD proteins play versatile roles in regulating signal transduction.
• This review offers insights into therapeutic strategies targeting CARD-containing proteins.