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Allantopyrone A interferes with the degradation of hypoxia-inducible factor 1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells

The Journal of Antibiotics volume 76, pages 324–334 (2023)Cite this article

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Abstract

Allantopyrone A is an α-pyrone metabolite that was originally isolated from the endophytic fungus Allantophomopsis lycopodina KS-97. We previously demonstrated that allantopyrone A exhibits anti-cancer, anti-inflammatory, and neuroprotective activities. In the present study, we showed that allantopyrone A up-regulated the protein expression of hypoxia-inducible factor (HIF)-1α in human fibrosarcoma HT-1080 cells. It also up-regulated the mRNA expression of BNIP3 and ENO1, but not other HIF target genes or HIF1A. Allantopyrone A did not inhibit the prolyl hydroxylation of HIF-1α, but enhanced the ubiquitination of cellular proteins. Consistent with this result, chymotrypsin-like and trypsin-like proteasome activities were reduced, but not completely inactivated by allantopyrone A. Allantopyrone A decreased the amount of proteasome catalytic subunits. Therefore, the present results showed that allantopyrone A interfered with the degradation of HIF-1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells.

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Acknowledgements

The authors would like to thank Dr. Takehiro Suzuki (RIKEN CSRS) and Dr. Naoshi Dohmae (RIKEN CSRS) for protein identification. This work was partly supported by JSPS KAKENHI Grant number 19H02885 (to T.K.).

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Authors and Affiliations

  1. Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan

    Chiharu Okuda, Yuto Ueda, Kenji Takeda, Koichiro Kawaguchi & Takao Kataoka

  2. Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan

    Makoto Muroi

  3. Chemical Resource Development Research Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan

    Makoto Muroi, Emiko Sanada & Hiroyuki Osada

  4. Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

    Hiroyuki Osada

  5. Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Yamagata, Japan

    Yoshihito Shiono

  6. The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan

    Ken-ichi Kimura

  7. Biomedical Research Center, Kyoto Institute of Technology, Kyoto, Japan

    Takao Kataoka

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  1. Chiharu Okuda
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Okuda, C., Ueda, Y., Muroi, M. et al. Allantopyrone A interferes with the degradation of hypoxia-inducible factor 1α protein by reducing proteasome activity in human fibrosarcoma HT-1080 cells. J Antibiot 76, 324–334 (2023). https://doi.org/10.1038/s41429-023-00610-5

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