HILPS , a long noncoding RNA essential for global oxygen sensing in humans.
In: Science advances, Jg. 9 (2023-11-24), Heft 47, S. eadi1867
academicJournal
Zugriff:
Adaptation to low levels of oxygen (hypoxia) is a universal biological feature across metazoans. However, the unique mechanisms how different species sense oxygen deprivation remain unresolved. Here, we functionally characterize a novel long noncoding RNA (lncRNA), LOC105369301 , which we termed hypoxia-induced lncRNA for polo-like kinase 1 (PLK1) stabilization ( HILPS ). HILPS exhibits appreciable basal expression exclusively in a wide variety of human normal and cancer cells and is robustly induced by hypoxia-inducible factor 1α (HIF1α). HILPS binds to PLK1 and sequesters it from proteasomal degradation. Stabilized PLK1 directly phosphorylates HIF1α and enhances its stability, constituting a positive feed-forward circuit that reinforces oxygen sensing by HIF1α. HILPS depletion triggers catastrophic adaptation defect during hypoxia in both normal and cancer cells. These findings introduce a mechanism that underlies the HIF1α identity deeply interconnected with PLK1 integrity and identify the HILPS -PLK1-HIF1α pathway as a unique oxygen-sensing axis in the regulation of human physiological and pathogenic processes.
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HILPS , a long noncoding RNA essential for global oxygen sensing in humans.
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Autor/in / Beteiligte Person: | Chen, Z ; Chen, C ; Xiao, L ; Tu, R ; Yu, M ; Wang, D ; Kang, W ; Han, M ; Huang, H ; Liu, H ; Zhao, B ; Qing, G |
Zeitschrift: | Science advances, Jg. 9 (2023-11-24), Heft 47, S. eadi1867 |
Veröffentlichung: | Washington, DC : American Association for the Advancement of Science, [2015]-, 2023 |
Medientyp: | academicJournal |
ISSN: | 2375-2548 (electronic) |
DOI: | 10.1126/sciadv.adi1867 |
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