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

Abstract

CARD subfamily is the second largest subfamily in the DD superfamily that plays important roles in regulating various signaling pathways, including but not limited to NF-kB activation signaling, apoptosis signaling and inflammatory signaling. The CARD subfamily contains 33 human CARD-containing proteins, regulating the assembly of many signaling complexes, including apoptosome, inflammsome, nodosome, the CBM complex, PIDDosome, the TRAF2 complex, and the MAVS signalosome, by homotypic CARD-CARD interactions. The mechanism of how CARDs find the right binding partner to form a specific complex remains unclear. This review uses different classification schemes to update the classification of CARD-containing proteins. Combining the classification based on domain structures, functions, associated signaling complexes, and roles would help better understand the structural and function diversity of CARD-containing proteins. This review also summarizes recent structural studies on CARDs. Especially, the CARD-containing complexes can be divided into the homodimeric, heterodimeric, oligomeric, filamentous CARD complexes and the CARD-ubiquitin complex. This review will give an overview of the versatile roles of CARDs in regulating signaling transduction, as well as the therapeutic drugs targeting CARD-containing proteins.

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal–Regulating Kinase 1

“…Caspase recruitment domain protein 6 (Card6) is a typical member of the CARD family, which is known to form large complexes through the CARD domain to regulate apoptosis and inflammation. (11) Indeed, Card6 interacts with receptor interacting serine/threonine protein kinase 2 (RIPK2), a member of the CARD family, to activate nuclear factor kappa B (NF-κB) signaling. (12,13) Card6 also shares structural features with the interferon-inducible guanosine triphosphatase (GTPase) family and can be induced by interferon in bone marrow-derived macrophages, B cells, T cells, and splenocytes.…”

“…Caspase recruitment domain protein 6 (Card6) is a typical member of the CARD family, which is known to form large complexes through the CARD domain to regulate apoptosis and inflammation . Indeed, Card6 interacts with receptor interacting serine/threonine protein kinase 2 (RIPK2), a member of the CARD family, to activate nuclear factor kappa B (NF‐κB) signaling .…”

Protective effect of epigallocatechin gallate, a major constituent of green tea, against renal ischemia–reperfusion injury in rats

“…Mitogen-activated protein kinase (MAPK) is a traditional signal pathway that plays an important role in regulating NF-κB activation in renal ischemia–reperfusion injury [ 4 ]. Moreover, NF-κB activation can induce inflammation and cell apoptosis [ 5 ]. Therefore, regulating MAPK signaling pathway may be a promising intervention to decrease renal I/R injury.…”

Picking up a Fight: Fine Tuning Mitochondrial Innate Immune Defenses Against RNA Viruses

“…Mitochondria play an important role in antiviral immunity by eliciting and maintaining the RLR/MAVS signaling cascade. RLRs are soluble RNA helicase type receptors containing N-terminal tandem of caspase activation and recruitment domains (CARDs) and a DECH-helicase domain required for RNA binding and ATP hydrolysis ( Kao et al, 2015 ; Brisse and Ly, 2019 ). All the three known RLRs (i.e., RIG-I, MDA-5, and LGP-2) are very efficient in distinguishing between cellular RNAs from those produced by RNA viruses ( Züst et al, 2011 ).…”