The Autoimmune Regulator (AIRE) Is a DNA-binding Protein

Pradeep G. Kumar, Malini Laloraya, Cong Yi Wang, Quin Guo Ruan, Abdoreza Davoodi-Semiromi, Kuo Jang Kao, Jin-Xiong She

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)41357-41364
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number44
DOIs
StatePublished - Nov 2 2001
Externally publishedYes

Fingerprint

DNA-Binding Proteins
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Proteins
Tandem Repeat Sequences
DNA
Zinc Fingers
Threonine
Transcription
Cytoplasmic and Nuclear Receptors
Dimers
Serine
Protein Kinase C
Tyrosine
Zinc
Assays
Monomers
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kumar, P. G., Laloraya, M., Wang, C. Y., Ruan, Q. G., Davoodi-Semiromi, A., Kao, K. J., & She, J-X. (2001). The Autoimmune Regulator (AIRE) Is a DNA-binding Protein. Journal of Biological Chemistry, 276(44), 41357-41364. https://doi.org/10.1074/jbc.M104898200

The Autoimmune Regulator (AIRE) Is a DNA-binding Protein. / Kumar, Pradeep G.; Laloraya, Malini; Wang, Cong Yi; Ruan, Quin Guo; Davoodi-Semiromi, Abdoreza; Kao, Kuo Jang; She, Jin-Xiong.

In: Journal of Biological Chemistry, Vol. 276, No. 44, 02.11.2001, p. 41357-41364.

Research output: Contribution to journalArticle

Kumar, PG, Laloraya, M, Wang, CY, Ruan, QG, Davoodi-Semiromi, A, Kao, KJ & She, J-X 2001, 'The Autoimmune Regulator (AIRE) Is a DNA-binding Protein', Journal of Biological Chemistry, vol. 276, no. 44, pp. 41357-41364. https://doi.org/10.1074/jbc.M104898200
Kumar PG, Laloraya M, Wang CY, Ruan QG, Davoodi-Semiromi A, Kao KJ et al. The Autoimmune Regulator (AIRE) Is a DNA-binding Protein. Journal of Biological Chemistry. 2001 Nov 2;276(44):41357-41364. https://doi.org/10.1074/jbc.M104898200
Kumar, Pradeep G. ; Laloraya, Malini ; Wang, Cong Yi ; Ruan, Quin Guo ; Davoodi-Semiromi, Abdoreza ; Kao, Kuo Jang ; She, Jin-Xiong. / The Autoimmune Regulator (AIRE) Is a DNA-binding Protein. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 44. pp. 41357-41364.
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