Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner

Hiroko Akiyoshi, Shigetsugu Hatakeyama, Jukka Pitkänen, Yasuhiro Mouri, Vassilis Doucas, Jun Kudoh, Kyoko Tsurugaya, Daisuke Uchida, Akemi Matsushima, Kiyotaka Oshikawa, Keiichi Nakayama, Nobuyoshi Shimizu, Pärt Peterson, Mitsuru Matsumoto

Research output: Contribution to journalArticle

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Abstract

Autoimmune regulator (AIRE) is responsible for the development of organ-specific autoimmune disease in a monogenic fashion. Rare and low levels of tissue expression together with the lack of AIRE-expressing cell lines have hampered a detailed analysis of the molecular dynamics of AIRE. Here we have established cell lines stably transfected with AIRE and studied the regulatory mechanisms for its subcellular expression. We found that nuclear body (NB) formation by AIRE was dependent on the cell cycle. Biochemical fractionation revealed that a significant proportion of AIRE is associated with the nuclear matrix, which directs the functional domains of chromatin to provide sites for gene regulation. Upon proteasome inhibition, AIRE NBs were increased with concomitant reduced expression in the cytoplasm, suggesting that subcellular targeting of AIRE is regulated by a ubiquitin-proteasome pathway. We also found that AIRE NBs compete for cAMP-response element-binding protein-binding protein/p300, a common coactivator of transcription, with the promyelocytic leukemia gene product. These results suggest that the transcriptional regulating activities of AIRE within a cell are controlled and organized in a spatiotemporal manner.

Original languageEnglish
Pages (from-to)33984-33991
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number32
DOIs
Publication statusPublished - Aug 6 2004

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Proteasome Endopeptidase Complex
Cells
Nuclear Matrix
Cell Line
Cyclic AMP Response Element-Binding Protein
Molecular Dynamics Simulation
Ubiquitin
Protein Binding
Genes
Autoimmune Diseases
Chromatin
Cell Cycle
Carrier Proteins
Cytoplasm
Leukemia
Transcription
Fractionation
Gene expression
Molecular dynamics
Tissue

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Akiyoshi, H., Hatakeyama, S., Pitkänen, J., Mouri, Y., Doucas, V., Kudoh, J., ... Matsumoto, M. (2004). Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. Journal of Biological Chemistry, 279(32), 33984-33991. https://doi.org/10.1074/jbc.M400702200

Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. / Akiyoshi, Hiroko; Hatakeyama, Shigetsugu; Pitkänen, Jukka; Mouri, Yasuhiro; Doucas, Vassilis; Kudoh, Jun; Tsurugaya, Kyoko; Uchida, Daisuke; Matsushima, Akemi; Oshikawa, Kiyotaka; Nakayama, Keiichi; Shimizu, Nobuyoshi; Peterson, Pärt; Matsumoto, Mitsuru.

In: Journal of Biological Chemistry, Vol. 279, No. 32, 06.08.2004, p. 33984-33991.

Research output: Contribution to journalArticle

Akiyoshi, H, Hatakeyama, S, Pitkänen, J, Mouri, Y, Doucas, V, Kudoh, J, Tsurugaya, K, Uchida, D, Matsushima, A, Oshikawa, K, Nakayama, K, Shimizu, N, Peterson, P & Matsumoto, M 2004, 'Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner', Journal of Biological Chemistry, vol. 279, no. 32, pp. 33984-33991. https://doi.org/10.1074/jbc.M400702200
Akiyoshi H, Hatakeyama S, Pitkänen J, Mouri Y, Doucas V, Kudoh J et al. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. Journal of Biological Chemistry. 2004 Aug 6;279(32):33984-33991. https://doi.org/10.1074/jbc.M400702200
Akiyoshi, Hiroko ; Hatakeyama, Shigetsugu ; Pitkänen, Jukka ; Mouri, Yasuhiro ; Doucas, Vassilis ; Kudoh, Jun ; Tsurugaya, Kyoko ; Uchida, Daisuke ; Matsushima, Akemi ; Oshikawa, Kiyotaka ; Nakayama, Keiichi ; Shimizu, Nobuyoshi ; Peterson, Pärt ; Matsumoto, Mitsuru. / Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 32. pp. 33984-33991.
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