Skip to Content
Merck
  • Dual functions of Aire CARD multimerization in the transcriptional regulation of T cell tolerance.

Dual functions of Aire CARD multimerization in the transcriptional regulation of T cell tolerance.

Nature communications (2020-04-04)
Yu-San Huoh, Bin Wu, Sehoon Park, Darren Yang, Kushagra Bansal, Emily Greenwald, Wesley P Wong, Diane Mathis, Sun Hur
ABSTRACT

Aggregate-like biomolecular assemblies are emerging as new conformational states with functionality. Aire, a transcription factor essential for central T cell tolerance, forms large aggregate-like assemblies visualized as nuclear foci. Here we demonstrate that Aire utilizes its caspase activation recruitment domain (CARD) to form filamentous homo-multimers in vitro, and this assembly mediates foci formation and transcriptional activity. However, CARD-mediated multimerization also makes Aire susceptible to interaction with promyelocytic leukemia protein (PML) bodies, sites of many nuclear processes including protein quality control of nuclear aggregates. Several loss-of-function Aire mutants, including those causing autoimmune polyendocrine syndrome type-1, form foci with increased PML body association. Directing Aire to PML bodies impairs the transcriptional activity of Aire, while dispersing PML bodies with a viral antagonist restores this activity. Our study thus reveals a new regulatory role of PML bodies in Aire function, and highlights the interplay between nuclear aggregate-like assemblies and PML-mediated protein quality control.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2-Peroxidase (HRP) antibody produced in mouse, clone M2, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Nitrilotriacetic acid disodium salt, Sigma Grade, ≥99%
Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Sigma-Aldrich
Rimiducid, ≥90% (HPLC)