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

26Citations
Citations of this article
43Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

Cite

CITATION STYLE

APA

Huoh, Y. S., Wu, B., Park, S., Yang, D., Bansal, K., Greenwald, E., … Hur, S. (2020). Dual functions of Aire CARD multimerization in the transcriptional regulation of T cell tolerance. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-15448-w

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free