Evidence map›Paper›PMID 37400498›Full record

ArticleNature cell biology2023

Prolonged hypoxia alleviates prolyl hydroxylation-mediated suppression of RIPK1 to promote necroptosis and inflammation.

Tao Zhang, Daichao Xu, Jianping Liu, Min Wang, Li-Juan Duan, Min Liu, Huyan Meng, Yuan Zhuang, Huibing Wang, Yingnan Wang and 29 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
13.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 58 citations in OpenAlex.

  1. Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026
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  15. Advances inMicroorganisms · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors at 9 institutions in 3 countries.

Tao Zhang *Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0009-0004-1704-1455
Daichao Xu *Interdisciplinary Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. xudaichao@sioc.ac.cn.ORCID 0000-0002-3286-4968
Jianping Liu *State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-7090-2112
Min Wang *Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Li-Juan DuanCenter for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT, USA.
Min LiuTransfusion Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Huyan MengF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0003-1511-6156
Yuan ZhuangDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Huibing WangDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Yingnan WangDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mingming LvDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4401-7464
Zhengyi ZhangDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9885-0817
Jia HuDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Linyu ShiInterdisciplinary Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Rui GuoInterdisciplinary Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Xingxing XieInterdisciplinary Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Hui LiuDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Emily EricksonDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yaru WangState Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0001-8300-0847
Wenyu YuDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Fabin DangDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1954-8231
Dongxian GuanDivision of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Cong JiangDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Xiaoming DaiDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9671-8137
Hiroyuki InuzukaDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Peiqiang YanDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jingchao WangDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mrigya BabutaDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8420-4796
Gewei LianDepartment of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Zhenbo TuDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3720-7844
Ji MiaoDivision of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0869-4492
Gyongyi SzaboDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Guo-Hua FongCenter for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT, USA.
Antoine E KarnoubDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yu-Ru LeeInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.ORCID 0000-0001-6592-6806
Lifeng PanState Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0002-9229-6288
William G KaelinDepartment of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0574-4856
Junying YuanInterdisciplinary Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. Junying_yuan@sioc.ac.cn.ORCID 0000-0003-2405-6036
Wenyi WeiDepartment of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. wwei2@bidmc.harvard.edu.ORCID 0000-0003-0512-3811
Beth Israel Deaconess Medical Center · USBoston Children's Hospital · USChinese Academy of Sciences · CNHarvard University · USBrigham and Women's Hospital · USShanghai Institute of Organic Chemistry · CNUConn Health · USBroad Institute · USInstitute of Biomedical Sciences, Academia Sinica · TW

Funding

The von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable MutationsR35CA210068 · NCI · DANA-FARBER CANCER INST · PI WILLIAM G. KAELIN · 2016 to 2026
$10.8M
Deciphering the physiological role and interplay between ubiquitination and phosphorylation pathways to guide targeted cancer therapiesR35CA253027 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wenyi Wei · 2020 to 2026
$6.2M
Novel regulation of PI3K/Akt to direct targeted breast cancer therapiesR01CA177910 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2013 to 2023
$3.9M
Role of TAZ in metabolic regulation in both normal and insulin resistant statesR01DK124328 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2021 to 2025
$2.2M
Copper and copper-binding proteins in insulin resistance-associated metabolic diseaseR01DK133331 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2022 to 2025
$1.9M
NCI NIH HHS R01 CA177910NCI NIH HHS R35 CA210068NCI NIH HHS R35 CA253027NIDDK NIH HHS R01 DK124328NIDDK NIH HHS R01 DK133331
6 · The paper itself

Abstract

The prolyl hydroxylation of hypoxia-inducible factor 1α (HIF-1α) mediated by the EGLN-pVHL pathway represents a classic signalling mechanism that mediates cellular adaptation under hypoxia. Here we identify RIPK1, a known regulator of cell death mediated by tumour necrosis factor receptor 1 (TNFR1), as a target of EGLN1-pVHL. Prolyl hydroxylation of RIPK1 mediated by EGLN1 promotes the binding of RIPK1 with pVHL to suppress its activation under normoxic conditions. Prolonged hypoxia promotes the activation of RIPK1 kinase by modulating its proline hydroxylation, independent of the TNFα-TNFR1 pathway. As such, inhibiting proline hydroxylation of RIPK1 promotes RIPK1 activation to trigger cell death and inflammation. Hepatocyte-specific Vhl deficiency promoted RIPK1-dependent apoptosis to mediate liver pathology. Our findings illustrate a key role of the EGLN-pVHL pathway in suppressing RIPK1 activation under normoxic conditions to promote cell survival and a model by which hypoxia promotes RIPK1 activation through modulating its proline hydroxylation to mediate cell death and inflammation in human diseases, independent of TNFR1.

Indexed as

NecroptosisReceptors, Tumor Necrosis Factor, Type IHumansHydroxylationHypoxiaHypoxia-Inducible Factor 1, alpha SubunitInflammationProlineReceptor-Interacting Protein Serine-Threonine KinasesHypoxia-Inducible Factor 1, alpha SubunitProlineReceptor-Interacting Protein Serine-Threonine KinasesReceptors, Tumor Necrosis Factor, Type IRIPK1 protein, human

Identifiers

PMID37400498
PMCPMC10617019
OpenAlexW4382937126

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.