Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

HIF hydroxylation and cellular oxygen sensing.

Eric Metzen1, Peter J Ratcliffe

  • 1Institute of Physiology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. metzen@physio.uni-luebeck.de

Biological Chemistry
|May 12, 2004
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

P53 - a new player in the metabolic adaptation of colorectal carcinoma cells under hypoxia.

BMC cancer·2026
Same author

Hypoxic regulation of chromatin and gene transcription.

Communications biology·2026
Same author

HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesis.

Nature communications·2025
Same author

Nitric oxide promotes cysteine N-degron proteolysis through control of oxygen availability.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Making sense of oxygen sensing.

The EMBO journal·2025
Same author

Hypoxia-Inducible Factor 2α: at the Interface between Oxygen Sensing Systems in Physiology and Pathology.

Physiology (Bethesda, Md.)·2025
Same journal

Neuronal membrane organization by the submembranous spectrin-ankyrin scaffold: evolution, specialization and disease.

Biological chemistry·2026
Same journal

Golgi-associated membrane scaffolds: roles in health and disease.

Biological chemistry·2026
Same journal

Mechanistic insights on spatiotemporal control of Ras-signaling.

Biological chemistry·2026
Same journal

Cysteine cathepsin proteases in apicomplexan parasites.

Biological chemistry·2026
Same journal

Electron donating and withdrawing groups affect the antioxidant activity of 4'-aminochalcones on gentamicin-induced kidney cell injury.

Biological chemistry·2026
Same journal

CNKSR2 scaffold function in the mammalian nervous system.

Biological chemistry·2026
See all related articles

Hypoxia-inducible factor (HIF) hydroxylases regulate cellular responses to low oxygen. These enzymes, including PHD1-3 and FIH, control HIF-alpha stability and activity, acting as key oxygen sensors.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Physiology

Background:

  • Hypoxia-inducible factor (HIF) is a critical transcriptional complex mediating cellular and systemic responses to hypoxia.
  • HIF activity is tightly regulated by oxygen-dependent enzymatic hydroxylations of HIF-alpha subunits.

Purpose of the Study:

  • To elucidate the mechanisms of HIF regulation by specific hydroxylases.
  • To understand the role of HIF prolyl and asparaginyl hydroxylation in oxygen sensing.

Main Methods:

  • Analysis of HIF-alpha subunits using structural and genetic approaches.
  • Identification of 2-oxoglutarate-dependent dioxygenases (PHD1-3 and FIH) as key hydroxylating enzymes.
  • Investigation of substrate interactions and cellular localization.

Related Experiment Videos

Main Results:

  • HIF prolyl hydroxylation by PHD1-3 targets HIF-alpha for proteasomal degradation via pVHL interaction.
  • HIF asparaginyl hydroxylation by FIH inhibits HIF-alpha interaction with the p300 co-activator.
  • Both hydroxylation pathways are crucial for regulating the HIF transcriptional cascade and cellular oxygen sensing.

Conclusions:

  • HIF hydroxylases (PHD1-3 and FIH) are central to cellular oxygen sensing.
  • Regulation of hydroxylase activity, protein levels, and co-substrate availability fine-tunes hypoxic responses.
  • These enzymes represent critical targets for understanding and potentially manipulating hypoxia-related pathways.