ISGylation directly modifies hypoxia-inducible factor-2α and enhances its polysome association.

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gaelan Melanson, Antonia C Du Bois, Caroline Webster, James Uniacke
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引用次数: 0

Abstract

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.

isg酰化直接修饰缺氧诱导因子-2α并增强其多体关联。
缺氧诱导因子(HIF)-1α和HIF-2α是发育和肿瘤扩张等环境中转录程序的中心调节因子。HIF-2α作为帽依赖的翻译因子。我们提供了新的见解,干扰素刺激基因15 (ISG15),一个泛素样修饰物,和hif如何在缺氧和干扰素诱导的细胞中相互调节。我们发现,在isg酰化诱导和HIF-α稳定的过程中,HIF-α都通过转录和/或转录后途径促进蛋白isg酰化。我们发现了ISG15修饰HIF-2α的第一个证据。isg酰化诱导HIF转录程序的系统水平改变,并增加HIF-2α的细胞质/核分数和翻译活性。这项工作确定了ISG15作为缺氧mRNA翻译的调节因子,这对免疫过程和疾病进展具有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
6.60
自引率
2.90%
发文量
303
审稿时长
1 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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