CARD tricks: controlling the interactions of CARD6 with RICK and microtubules.
In recent years, a number of proteins have been identified that contain a homotypic interaction motif called the caspase recruitment domain (CARD). Most proteins containing a CARD are involved in pathways regulating apoptosis or adaptive or innate immunity. Examples of prominent CARD proteins are caspase-9 and Apaf1, which are involved in the intrinsic death pathway; BCL10 and CARD11, which mediate antigen receptor-induced NF-kappaB activation; and receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory protein kinase (RICK) and the nucleotide-binding oligomerization domain (NOD) proteins, which induce NF-kappaB activation in response to intracellular bacterial peptidoglycan. The most recently discovered pathway involving CARD proteins senses virally-derived double-stranded (ds) RNA and initiates a host defense signaling program. CARD6 is a CARD-containing protein with a domain structure not shared by any other CARD protein. Although the CARD6 cDNA was deposited in GenBank five years ago, the physiological function of full-length CARD6 has yet to be reported. Here we review our initial characterization of CARD6 and discuss the functional implications of various conserved modules found in the CARD6 protein sequence. We conclude that CARD6 is structurally and potentially functionally related to the superfamily of interferon (IFN)-inducible GTPases, a growing family of host defense proteins that confer cell-autonomous immunity.
Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, Canada.
Almut
A
Dufner
Tak W
TW
Mak
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C478017:CARD6 protein, human; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse