Allantopyrone A是一种α-羟基酮代谢物，最初是从内生真菌Allantophomopsis lycopodina KS-97中分离出来的。我们先前证明了allantopyrone A具有抗癌，抗炎和神经保护作用。在本研究中，我们表明allantopyrone A在人成纤维肉瘤HT-1080细胞中上调了缺氧诱导因子（HIF）-1α的蛋白表达。它还上调了BNIP3和ENO1的mRNA表达，但不上调其他HIF靶基因或HIF1A。Allantopyrone A没有抑制HIF-1α的脯氨酸羟化，但增强了细胞蛋白的泛素化。与此结果一致，chymotrypsin-like和trypsin-like蛋白酶体活性被减少，但没有被完全失活。Allantopyrone A减少了蛋白酶体催化亚基的数量。因此，本研究结果表明allantopyrone A通过减少人成纤维肉瘤HT-1080细胞中的蛋白酶体活性干扰HIF-1α蛋白的降解。 ©2023.作者（含）,独家许可日本抗生素研究协会。

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.© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.