Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner

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

研究成果: Article

51 引用 (Scopus)

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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.

元の言語English
ページ(範囲)33984-33991
ページ数8
ジャーナルJournal of Biological Chemistry
279
発行部数32
DOI
出版物ステータスPublished - 2004 8 6

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ASJC Scopus subject areas

  • Biochemistry

これを引用

Akiyoshi, H., Hatakeyama, S., Pitkänen, J., Mouri, Y., Doucas, V., Kudo, 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