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- Title
Oligomerized CARD16 promotes caspase-1 assembly and IL-1β processing.
- Authors
Karasawa, Tadayoshi; Kawashima, Akira; Usui, Fumitake; Kimura, Hiroaki; Shirasuna, Koumei; Inoue, Yoshiyuki; Komada, Takanori; Kobayashi, Motoi; Mizushina, Yoshiko; Sagara, Junji; Takahashi, Masafumi
- Abstract
Increasing evidence indicates that caspase recruitment domain (CARD)-mediated caspase-1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)-1β 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-1β release. In contrast, CARD17 did not form a homo-oligomer or filaments and inhibited CASP1-dependent IL-1β release. Mutated CARD16 D27G , mimicking the CARD17 amino acid sequence, formed a homo-oligomer but failed to form a filament-like structure. Consequently, CARD16 D27G weakly promoted CASP1 filament assembly and subsequent IL-1β release. These results suggest that oligomerized CARD16 promotes CARD-mediated molecular assembly and CASP1 activation.
- Subjects
CASPASES; INTERLEUKIN-1; OLIGOMERIZATION; INFLAMMATION; HOMOLOGY (Biochemistry); APOPTOSIS
- Publication
FEBS Open Bio, 2015, Vol 5, p348
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1016/j.fob.2015.04.011