The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system

Masahide Tojo, Kazuhito Matsuzaki, Takeshi Minami, Yoshiomi Honda, Hideyo Yasuda, Tsutomu Chiba, Hideyuki Saya, Yoshiaki Fujii-Kuriyama, Mitsuyoshi Nakao

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Abstract

The aryl hydrocarbon receptor nuclear transporter (ARNT) is a member of the basic helix-loop-helix/PAS (Per-ARNT-Sim) family of transcription factors, which are important for cell regulation in response to environmental conditions. ARNT is an indispensable partner of the aryl hydrocarbon receptor (AHR) or hypoxia-inducible factor-1α. This protein is also able to form homodimers such as ARNT/ARNT. However, the molecular mechanism that regulates the transcriptional activity of ARNT remains to be elucidated. Here, we report that ARNT is modified by SUMO-1 chiefly at Lys245 within the PAS domain of this protein, both in vivo and in vitro. Substitution of the target lysine with alanine enhanced the transcriptional potential of ARNT per se. Furthermore, green fluorescent protein-fused ARNT tended to form nuclear foci in ∼20% of the transfected cells, and the foci partly colocalized with PML nuclear bodies. PML, one of the well known substrates for sumoylation, was found to augment the transcriptional activities of ARNT. ARNT bound AHR or PML, whereas the sumoylated form of ARNT associated with AHR, but not with PML, resulting in a reduced effect of PML, on transactivation by ARNT. Our data suggest that the sumoylation of ARNT modulates its transcriptional role through affecting the ability of ARNT to interact with cooperative molecules such as PML. This exemplifies a crucial role of protein sumoylation in modulating protein-protein interactions.

Original languageEnglish
Pages (from-to)46576-46585
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number48
DOIs
Publication statusPublished - 2002 Nov 29
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Tojo, M., Matsuzaki, K., Minami, T., Honda, Y., Yasuda, H., Chiba, T., Saya, H., Fujii-Kuriyama, Y., & Nakao, M. (2002). The aryl hydrocarbon receptor nuclear transporter is modulated by the SUMO-1 conjugation system. Journal of Biological Chemistry, 277(48), 46576-46585. https://doi.org/10.1074/jbc.M205987200