BRISC complex deubiquitinates NLRP3

Stable Identifier
R-HSA-5691439
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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As part of the cytosolic BRISC complex (Cooper et al. 2009), BRCC3 regulates NLRP3 activity by promoting K63-deubiquitination of its LRR domain (Py et al. 2013). FAM175B (ABRO1), another BRISC subunit, binds directly to NLRP3 leading to FAM175B-dependent recruitment of the BRISC complex which mediates deubiquitination of NLRP3 upon inflammasome activation (Ren G et al.2019). In addition, FAM175B (ABRO1) enhanced BRCC3 protein stability by inhibiting WWP2-mediated ubiquitination and degradation of BRCC3 through the ubiquitin-proteasome pathway (Zhang W et al. 2021).The consequent activation of NLRP3 has been proposed to mediate necrotic cell sensing and the subsequent release of the proinflammatory cytokine IL-1Beta after hypoxic injury (Iyer et al. 2009).

Literature References
PubMed ID Title Journal Year
23246432 Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity

Kim, MS, Vakifahmetoglu-Norberg, H, Yuan, J, Py, BF

Mol. Cell 2013
Participants
Participates
Catalyst Activity

Lys63-specific deubiquitinase activity of BRISC complex:K63polyUb-NLRP3 [cytosol]

Orthologous Events
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