Abstract
Proteins possessing the caspase recruitment domain (CARD) motif have been implicated in pathways leading to activation of caspases or NF-kappaB in the context of apoptosis or inflammation, respectively. Here we report the identification of a novel protein, CARDINAL, that contains a CARD motif and also exhibits a high degree of homology to the C terminus of DEFCAP/NAC, a recently described member of the Apaf-1/Nod-1 family. In contrast with the majority of CARD proteins described to date, CARDINAL failed to promote apoptosis or NF-kappaB activation. Rather, CARDINAL potently suppressed NF-kappaB activation associated with overexpression of TRAIL-R1, TRAIL-R2, RIP, RICK, Bcl10, and TRADD, or through ligand-induced stimulation of the interleukin-1 or tumor necrosis factor receptors. Co-immunoprecipitation experiments revealed that CARDINAL interacts with the regulatory subunit of the IkappaB kinase (IKK) complex, IKKgamma (NEMO), providing a molecular basis for CARDINAL function. Thus, CARDINAL is a novel regulator of NF-kappaB activation in the context of pro-inflammatory signals.
Original language | English |
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Pages (from-to) | 44069-77 |
Number of pages | 9 |
Journal | The Journal of biological chemistry |
Volume | 276 |
Issue number | 47 |
DOIs | |
Publication status | Published - 23 Nov 2001 |
Keywords
- Adaptor Proteins, Signal Transducing
- Amino Acid Sequence
- CARD Signaling Adaptor Proteins
- Carrier Proteins/chemistry
- Caspases/metabolism
- Cell Line
- Humans
- Molecular Sequence Data
- NF-kappa B/chemistry
- Neoplasm Proteins
- Precipitin Tests
- Sequence Homology, Amino Acid
- Subcellular Fractions/metabolism