A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans.

ABSTRACT: Proteasomes are multisubunit proteases that play a critical role in maintaining cellular function through the selective degradation of ubiquitinated proteins. When 3 additional β subunits, expression of which is induced by IFN-γ, are substituted for their constitutively expressed counterparts, the structure is converted to an immunoproteasome. However, the underlying roles of immunoproteasomes in human diseases are poorly understood. Using exome analysis, we found a homozygous missense mutation (G197V) in immunoproteasome subunit, β type 8 (PSMB8), which encodes one of the β subunits induced by IFN-γ in patients from 2 consanguineous families. Patients bearing this mutation suffered from autoinflammatory responses that included recurrent fever and nodular erythema together with lipodystrop

SUBMITTER: Kitamura A 

PROVIDER: S-EPMC3195477 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature