Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer.

Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer.
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DOI:
10.3389/fonc.2017.00286
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发表时间:
2017
影响因子:
4.7
通讯作者:
Kurelac I
Kurelac I
中科院分区:
医学3区
文献类型:
--
作者:
Iommarini L;Porcelli AM;Gasparre G;Kurelac I

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缺氧诱导因子1 α(HIF-1α)协调细胞适应低氧和营养缺乏的环境,并推动人类实体癌向恶性发展。其典型调节涉及脯氨酰羟化酶(PHDs),其在常氧下诱导降解,而在缺氧下允许稳定HIF-1α。然而,在某些情况下,HIF-1α的调节超出了实际的外部氧水平,并涉及PHD独立的机制。在这里,我们收集并讨论了非经典的HIF-1α调节的证据,特别关注线粒体呼吸复合物损伤对这种多效性转录因子稳定性的影响。
Hypoxia-inducible factor 1 alpha (HIF-1α) orchestrates cellular adaptation to low oxygen and nutrient-deprived environment and drives progression to malignancy in human solid cancers. Its canonical regulation involves prolyl hydroxylases (PHDs), which in normoxia induce degradation, whereas in hypoxia allow stabilization of HIF-1α. However, in certain circumstances, HIF-1α regulation goes beyond the actual external oxygen levels and involves PHD-independent mechanisms. Here, we gather and discuss the evidence on the non-canonical HIF-1α regulation, focusing in particular on the consequences of mitochondrial respiratory complexes damage on stabilization of this pleiotropic transcription factor.
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