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 I. Nakayama, Nobuyoshi Shimizu, Pärt Peterson, Mitsuru Matsumoto

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 - 2004 Aug 6

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Akiyoshi, H., Hatakeyama, S., Pitkänen, J., Mouri, Y., Doucas, V., Kudoh, J., Tsurugaya, K., Uchida, D., Matsushima, A., Oshikawa, K., Nakayama, K. I., Shimizu, N., Peterson, P., & 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