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Oligomerized CARD16 promotes caspase-1 assembly and IL-1β processing

Tadayoshi Karasawa1, Akira Kawashima1, Fumitake Usui1

  • 1Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.

FEBS Open Bio
|May 15, 2015
PubMed

Insights

Oligomerization of CARD16 activates caspase-1 (CASP1) and promotes inflammation by forming filament-like structures. CARD17 inhibits CASP1 activation, highlighting distinct roles in inflammatory pathways.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Caspase recruitment domain (CARD)-mediated assembly of caspase-1 (CASP1) is crucial for inflammation via interleukin (IL)-1β release.
  • The precise molecular functions of CARD16 and CARD17, previously considered inhibitory CASP1 homologs, remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular function of CARD16 and CARD17 in CASP1 activation and IL-1β release.
  • To investigate the role of oligomerization and filament formation in CARD16-mediated CASP1 activation.

Main Methods:

  • Transient transfection of HeLa cells with CARD16 and CARD17.
  • Analysis of protein interactions, homo-oligomerization, and filament formation.
  • Assessment of CASP1 assembly and IL-1β release.

Main Results:

  • CARD16, unlike CARD17, forms homo-oligomers and filament-like structures with CASP1CARD.
  • Oligomerized CARD16 promotes CASP1 filament assembly and IL-1β release, initiating inflammation.
  • CARD17 inhibits CASP1-dependent IL-1β release, and a CARD16 mutant mimicking CARD17 showed impaired activation.

Conclusions:

  • Oligomerized CARD16 acts as a CASP1 activator by promoting CARD-mediated molecular assembly.
  • CARD16 and CARD17 exhibit opposing roles in regulating CASP1 activation and inflammatory responses.

Keywords:
ANOVA, analysis of varianceASC, apoptosis-associated speck-like protein containing a caspase recruitment domainBS3, bis(sulfosccinimidyl)suberateBcl10, B-cell lymphoma/leukemia 10CARD, caspase recruitment domainCARMA1, CARD-membrane-associated guanylate kinase 1CASP1, caspase-1COPs, CARD-only proteinsCaspaseCytokineELISA, enzyme-linked immunosorbent assayFCS, fetal calf serumIL, interleukinInflammationInterleukinLPS, lipopolysaccharideLRRs, leucine-rich repeatsNF-κB, nuclear factor kappa betaNLRs, nucleotide-binding domain leucine-rich repeat containing receptorsPYD, pyrin domain

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