TY - JOUR
T1 - The Autoimmune Regulator (AIRE) Is a DNA-binding Protein
AU - Kumar, Pradeep G.
AU - Laloraya, Malini
AU - Wang, Cong Yi
AU - Ruan, Quin Guo
AU - Davoodi-Semiromi, Abdoreza
AU - Kao, Kuo Jang
AU - She, Jin-Xiong
PY - 2001/11/2
Y1 - 2001/11/2
N2 - The autoimmune regulator (AIRE) protein is a putative transcription regulator with two plant homeodomain-type zinc fingers, a putative DNA-binding domain (SAND), and four nuclear receptor binding LXXLL motifs. We have shown here that in vitro, recombinant AIRE can form homodimers and homotetramers that were also detected in thymic protein extracts. Recombinant AIRE also oligomerizes spontaneously upon phosphorylation by cAMP dependent protein kinase A or protein kinase C. Similarly, thymic AIRE protein is phosphorylated at the tyrosine and serine/threonine residues. AIRE dimers and tetramers, but not the monomers, can bind to G-doublets with the ATTGGTTA motif and the TTATTA-box. Competition assays revealed that sequences with one TTATTA motif and two tandem repeats of ATTGGTTA had the highest binding affinity. These findings demonstrate that AIRE is an important DNA binding molecule involved in immune regulation.
AB - The autoimmune regulator (AIRE) protein is a putative transcription regulator with two plant homeodomain-type zinc fingers, a putative DNA-binding domain (SAND), and four nuclear receptor binding LXXLL motifs. We have shown here that in vitro, recombinant AIRE can form homodimers and homotetramers that were also detected in thymic protein extracts. Recombinant AIRE also oligomerizes spontaneously upon phosphorylation by cAMP dependent protein kinase A or protein kinase C. Similarly, thymic AIRE protein is phosphorylated at the tyrosine and serine/threonine residues. AIRE dimers and tetramers, but not the monomers, can bind to G-doublets with the ATTGGTTA motif and the TTATTA-box. Competition assays revealed that sequences with one TTATTA motif and two tandem repeats of ATTGGTTA had the highest binding affinity. These findings demonstrate that AIRE is an important DNA binding molecule involved in immune regulation.
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U2 - 10.1074/jbc.M104898200
DO - 10.1074/jbc.M104898200
M3 - Article
C2 - 11533054
AN - SCOPUS:0035798665
SN - 0021-9258
VL - 276
SP - 41357
EP - 41364
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -