Oligomerized CARD16 promotes caspase-1 assembly and IL-1ß processing.
FEBS Open Bio
; 5: 348-56, 2015.
Article
em En
| MEDLINE
| ID: mdl-25973362
Increasing evidence indicates that caspase recruitment domain (CARD)-mediated caspase-1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)-1ß release, leading to the initiation of inflammation. Both CARD16 and CARD17 were previously reported as inhibitory homologs of CASP1; however, their molecular function remains unclear. Here, we identified that oligomerization activity allows CARD16 to function as a CASP1 activator. We investigated the molecular characteristics of CARD16 and CARD17 in transiently transfected HeLa cells. Although both CARD16 and CARD17 interacted with CASP1CARD, only CARD16 formed a homo-oligomer. Oligomerized CARD16 formed a filament-like structure with CASP1CARD and a speck with apoptosis-associated speck-like protein containing a CARD. A filament-like structure formed by CARD16 promoted CASP1 filament assembly and IL-1ß release. In contrast, CARD17 did not form a homo-oligomer or filaments and inhibited CASP1-dependent IL-1ß release. Mutated CARD16D27G, mimicking the CARD17 amino acid sequence, formed a homo-oligomer but failed to form a filament-like structure. Consequently, CARD16D27G weakly promoted CASP1 filament assembly and subsequent IL-1ß release. These results suggest that oligomerized CARD16 promotes CARD-mediated molecular assembly and CASP1 activation.
ANOVA, analysis of variance; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; BS3, bis(sulfosccinimidyl)suberate; Bcl10, B-cell lymphoma/leukemia 10; CARD, caspase recruitment domain; CARMA1, CARD-membrane-associated guanylate kinase 1; CASP1, caspase-1; COPs, CARD-only proteins; Caspase; Cytokine; ELISA, enzyme-linked immunosorbent assay; FCS, fetal calf serum; IL, interleukin; Inflammation; Interleukin; LPS, lipopolysaccharide; LRRs, leucine-rich repeats; NF-κB, nuclear factor kappa beta; NLRs, nucleotide-binding domain leucine-rich repeat containing receptors; PYD, pyrin domain
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article