ArticleNature cell biology2012
The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
Article in Nature cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Pooled it
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- Beneficially Stressing the Peripheral Nervous System to Repair.International journal of molecular sciences · 2026Review
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- Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora.Biomedicines · 2024Review
- Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis.Clinical and translational medicine · 2024Article
- A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.Nature communications · 2024Article
- OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Clinical implications of activation of the LIMD1-VHL-HIF1α pathway during head-&-neck squamous cell carcinoma development.The Indian journal of medical research · 2024Article
- Targeting the Ajuba/Notch axis increases the sensitivity of colon cancer cells to 5-fluorouracil.CytoJournal · 2024Article
- Characterization of genetic variants in theHaematologica · 2023Article
- Comparative functional RNA editomes of neural differentiation from human PSCs.Life medicine · 2022Article
- Analysis of genome and methylation changes in Chinese indigenous chickens over time provides insight into species conservation.Communications biology · 2022Article
- Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa.Pathogens (Basel, Switzerland) · 2022Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Hypoxia inducible factor 1α inhibitor PX-478 reduces atherosclerosis in mice.Atherosclerosis · 2022Article
- HIF-1α switches the functionality of TGF-β signaling via changing the partners of smads to drive glucose metabolic reprogramming in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2021Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
There are three prolyl hydroxylases (PHD1, 2 and 3) that regulate the hypoxia-inducible factors (HIFs), the master transcriptional regulators that respond to changes in intracellular O(2) tension. In high O(2) tension (normoxia) the PHDs hydroxylate two conserved proline residues on HIF-1α, which leads to binding of the von Hippel-Lindau (VHL) tumour suppressor, the recognition component of a ubiquitin-ligase complex, initiating HIF-1α ubiquitylation and degradation. However, it is not known whether PHDs and VHL act separately to exert their enzymatic activities on HIF-1α or as a multiprotein complex. Here we show that the tumour suppressor protein LIMD1 (LIM domain-containing protein) acts as a molecular scaffold, simultaneously binding the PHDs and VHL, thereby assembling a PHD-LIMD1-VHL protein complex and creating an enzymatic niche that enables efficient degradation of HIF-1α. Depletion of endogenous LIMD1 increases HIF-1α levels and transcriptional activity in both normoxia and hypoxia. Conversely, LIMD1 expression downregulates HIF-1 transcriptional activity in a manner depending on PHD and 26S proteasome activities. LIMD1 family member proteins Ajuba and WTIP also bind to VHL and PHDs 1 and 3, indicating that these LIM domain-containing proteins represent a previously unrecognized group of hypoxic regulators.
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Registered trials
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.