Functional interaction of AIRE with PIAS1 in transcriptional regulation

• Published in: Molecular immunology Vol. 45; no. 7; pp. 1847 - 1862
• Main Authors: Ilmarinen, Tanja, Kangas, Hannele, Kytömaa, Taina, Eskelin, Petra, Saharinen, Juha, Seeler, Jacob-S., Tanhuanpää, Kimmo, Chan, Fiona Yih-Ling, Slattery, Robyn Maree, Alakurtti, Kirsi, Palvimo, Jorma J., Ulmanen, Ismo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2008
• Subjects: AIRE; AIRE Protein; Amino Acid Motifs; Animals; Cell Line; Cystatin B; Cystatin B (CSTB) promoter; Cystatins - genetics; Gene Expression Regulation; Humans; Insulin - genetics; Insulin promoter; Mice; Mutant Proteins - metabolism; Nuclear Matrix - metabolism; PIAS; Promoter Regions, Genetic - genetics; Protein Binding; Protein Inhibitors of Activated STAT - chemistry; Protein Inhibitors of Activated STAT - metabolism; Protein Processing, Post-Translational; Protein Structure, Tertiary; Protein Transport; Sequence Deletion; Small Ubiquitin-Related Modifier Proteins - metabolism; SP100; Subcellular Fractions - metabolism; SUMO; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation - genetics; Transfection; SP100; SUMO; AIRE; PIAS; Insulin promoter; Cystatin B (CSTB) promoter
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2007.10.045

AIRE (autoimmune regulator) promotes the establishment of self-tolerance by regulating gene expression in the thymus. Mutations in AIRE lead to an autoimmune disease, APECED. Here we have identified PIAS proteins as novel AIRE interaction partners. Although PIAS proteins function as E3 SUMO ligases, AIRE is not sumoylated. We expressed AIRE, wt PIAS1, and PIAS1 mutants with deleted SP-RING domain or SUMO interaction motif (SIM) in different cell lines and demonstrate that AIRE and PIAS1 localize to adjacent nuclear bodies (NBs). The expression of AIRE enhances the formation of PIAS1 NBs. The ability of PIAS1 to localize into NBs and interconnect with AIRE is neither dependent on the SP-RING domain nor the SIM. Further, we show that PIAS1 is able to attract AIRE into SUMO1-containing complexes and that the process is dependent on the SIM of PIAS1. PIAS1 and AIRE concurrently activate the human insulin promoter, a known target gene of AIRE, and the SP-RING is required for this activation. Moreover, AIRE represses and PIAS1 activates the CSTB promoter, used as a model for a housekeeping promoter, and both the SP-RING and SIM are needed for its activation by PIAS1. Collectively, our data suggest that AIRE and PIAS1 interact functionally to regulate the activities of the target genes of AIRE.