Autoimmune regulator (Aire) is a transcriptional regulator that controls negative selection of self-reactive T cells in the thymus. Aire achieves this goal by inducing the expression of peripheral tissue self-antigens in medullary thymic epithelial cells (mTECs). Incidentally, Aire forms large aggregate-like assemblies visualized as speckles in nucleus; however, the significance and function of these nuclear structures of Aire is unknown.
The research in collaboration with Prof. Sun Hur at Harvard Medical School, Boston demonstrated that CARD domain of Aire helps it in forming filamentous homo-multimers in vitro and this assembly is critical for Aire’s transcriptional activity. However, this assembly also makes Aire susceptible to interaction with promyelocytic leukemia (PML) bodies, the sites of protein quality control inside the nucleus. Interestingly, pathogenic Aire mutants form nuclear foci with increased PML body association. This study unraveled a new regulatory role of PML bodies in Aire function.
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