AIRE acetylation and deacetylation: effect on protein stability and transactivation activity

Journal of Biomedical Science

Maria Cristina Rosatelli³  Irene Messana²  Tiziana Cabras²  Luisella Saba³  Carla Cossu³  Alessandra Meloni¹  Maria Luisa Serra³  Federica Incani³ 

[1] Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy;Dipartimento di Scienze della Vita e dell¿Ambiente, Sezione di Biochimica, Università degli Studi di Cagliari, Cagliari, Italy;Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare, Unità di Ricerca di Scienze Biomediche e Biotecnologie, Università degli Studi di Cagliari, via Jenner s/n, Cagliari, Italy

关键词: HDAC1-HDAC2/SIN3A complex;    Mass spectrometry;    Deacetylation;    Acetylation;    Autoimmune regulator;   

Others  :  1146515
DOI  :  10.1186/s12929-014-0085-z

 received in 2014-06-17, accepted in 2014-08-16,  发布年份 2014

【 摘 要 】

Background

The AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in AIRE gene cause the autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population.

AIRE protein is primarily known as a transcriptional regulator and is capable of interacting with numerous proteins. The first characterized partner of AIRE is the ubiquitous transcription factor CREB-binding protein (CBP), which regulates DNA transcription through the acetylation and deacetylation of histones. More recently, the role of p300 in AIRE acetylation, which could influence the selection of AIRE activated genes, has been described.

Results

In this study, we have precisely mapped, by mass spectrometry experiments, the sites of protein acetylation and, by mutagenesis assays, we have described a set of acetylated lysines as being crucial in influencing the subcellular localization of AIRE. Furthermore, we have also determined that the de-acetyltransferase enzymes HDAC1-2 are involved in the lysine de-acetylation of AIRE.

Conclusions

On the basis of our results and those reported in literature, we propose a model in which lysines acetylation increases the stability of AIRE in the nucleus. In addition, we observed that the interaction of AIRE with deacetylases complexes inhibits its transcriptional activity and is probably responsible for the instability of AIRE, which becomes more susceptible to degradation in the proteasome.

【 授权许可】

   
2014 Incani et al.; licensee BioMed Central.

【 图 表 】

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