Caspase recruitment domain family member 6 (CARD6) is a protein-encoding gene. It contains a caspase recruitment domain (CARD) and is initially suggested to play a role in NF-κB activation [1,2,4]. It may be structurally related to the interferon (IFN)-inducible GTPases and could potentially be involved in immune-related functions [3,5].

In a SCI mouse model, CARD6 knockout significantly accelerated functional deficits, neuron death, and glia activation, while CARD6 overexpression had the opposite effects. This indicates that CARD6 is a suppressor of SCI, likely by inhibiting apoptosis, inflammation, and oxidative stress-associated ROS production [1]. In collagen-induced arthritis (CIA) mice, promoting CARD6 expression using adeno-associated virus (AAV) effectively attenuated the severity of arthritis, improved histopathological damage, and hindered bone erosion. It achieved this by suppressing the TNFR1/TRAF2 signaling pathway, which in turn inhibited the NF-κB pathway [2].

In conclusion, CARD6 plays important roles in multiple disease-related biological processes. Its function in suppressing spinal cord injury and collagen-induced rheumatoid arthritis has been revealed through mouse models. These findings suggest that CARD6 could potentially be a therapeutic target for treating spinal cord injury and rheumatoid arthritis.

References:

1. Wang, Jiang Lin, Luo, Xiao, Liu, Li. 2019. Targeting CARD6 attenuates spinal cord injury (SCI) in mice through inhibiting apoptosis, inflammation and oxidative stress associated ROS production. In Aging, 11, 12213-12235. doi:10.18632/aging.102561. https://pubmed.ncbi.nlm.nih.gov/31841440/

2. Zhao, Min, He, Hongying, Yin, Jianbao. 2020. CARD6 protects against collagen-induced rheumatoid arthritis in mice through attenuating the inflammatory response and joint destruction via suppression of TNFR1/TRAF2 signaling. In Biochemical and biophysical research communications, 526, 1092-1099. doi:10.1016/j.bbrc.2020.04.006. https://pubmed.ncbi.nlm.nih.gov/32317187/

3. Dufner, Almut, Mak, Tak W. 2006. CARD tricks: controlling the interactions of CARD6 with RICK and microtubules. In Cell cycle (Georgetown, Tex.), 5, 797-800. doi:. https://pubmed.ncbi.nlm.nih.gov/16582588/

4. Stehlik, Christian, Hayashi, Hideki, Pio, Frederick, Godzik, Adam, Reed, John C. 2003. CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways. In The Journal of biological chemistry, 278, 31941-9. doi:. https://pubmed.ncbi.nlm.nih.gov/12775719/

5. Dufner, Almut, Duncan, Gordon S, Wakeham, Andrew, Ohashi, Pamela S, Mak, Tak W. 2007. CARD6 is interferon inducible but not involved in nucleotide-binding oligomerization domain protein signaling leading to NF-kappaB activation. In Molecular and cellular biology, 28, 1541-52. doi:. https://pubmed.ncbi.nlm.nih.gov/18160713/