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Published on: July 14, 2016
Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis
B J Geddes1, L Wang, W J Huang
1Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
Insights
A new protein, CARD12, regulates programmed cell death (apoptosis) and inflammation. It interacts with ASC and caspase-1, suggesting a role in coordinating cell death and inflammatory signaling pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- The CED4/Apaf-1 protein family are key regulators of apoptosis and NF-kappaB signaling.
- Understanding novel members of this family is crucial for elucidating complex cellular processes.
Purpose of the Study:
- To identify and characterize a novel human member of the CED4/Apaf-1 protein family.
- To investigate the functional interactions and potential roles of this new protein in cellular signaling.
Main Methods:
- Protein identification and structural analysis.
- Expression studies in cells to assess apoptotic activity.
- Co-precipitation assays to identify interacting partners.
Main Results:
- A novel human protein, CARD12, was identified, structurally similar to CARD4.
- CARD12 induces apoptosis and its CARD domain interacts with ASC.
- CARD12 was found to coprecipitate with caspase-1.
Conclusions:
- CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis.
- CARD12 may function in a complex with ASC and caspase-1 to regulate both apoptotic and inflammatory signaling pathways.
Abstract:
The CED4/Apaf-1 family of proteins functions as critical regulators of apoptosis and NF-kappaB signaling pathways. A novel human member of this family, called CARD12, was identified that induces apoptosis when expressed in cells. CARD12 is most similar in structure to the CED4/Apaf-1 family member CARD4, and is comprised of an N-terminal caspase recruitment domain (CARD), a central nucleotide-binding site (NBS), and a C-terminal domain of leucine-rich repeats (LRR). The CARD domain of CARD12 interacts selectively with the CARD domain of ASC, a recently identified proapoptotic protein. In addition, CARD12 coprecipitates caspase-1, a caspase that participates in both apoptotic signaling and cytokine processing. CARD12 may assemble with proapoptotic CARD proteins to coordinate the activation of downstream apoptotic and inflammatory signaling pathways.
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