| Autor: |
Melanson, Gaelan, Du Bois, Antonia C., Webster, Caroline, Uniacke, James |
| Předmět: |
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| Zdroj: |
FEBS Letters; Nov2022, Vol. 596 Issue 21, p2834-2850, 17p |
| Abstrakt: |
The hypoxia‐inducible factors (HIF)‐1α and HIF‐2α are central regulators of transcriptional programmes in settings such as development and tumour expansion. HIF‐2α moonlights as a cap‐dependent translation factor. We provide new insights into how the interferon‐stimulated gene 15 (ISG15), a ubiquitin‐like modifier, and the HIFs regulate one another in hypoxia and interferon‐induced cells. We show that upon ISGylation induction and HIF‐α stabilization, both HIFs promote protein ISGylates through transcriptional and/or post‐transcriptional pathways. We show the first evidence of HIF‐2α modification by ISG15. ISGylation induces system‐level alterations to the HIF transcriptional programme and increases the cytoplasmic/nuclear fraction and translation activity of HIF‐2α. This work identifies ISG15 as a regulator of hypoxic mRNA translation, which has implications for immune processes and disease progression. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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