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. 2022 Jul 7;7:218. doi: 10.1038/s41392-022-01080-1

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — The underlying principles of hypoxia and cross-talk of HIF signal with multiple pathways. a Under normoxia, HIFs (α and β subunits) undergo ubiquitination mediated by PHDs (oxygen-dependent proline hydroxylase family) and pVHL (von Hippel–Lindau tumor suppressor protein). The enzymatic activity PHD is prohibited under hypoxia. HIFs are stabilized to promote downstream genes transcription. b The interaction among HIF signal with multiple signaling pathways