Ancient sensor

Ludwig Oxford’s Peter Ratcliffe is among the researchers who first discovered, about 20 years ago, how cells sense and respond to the availability of oxygen. That system centered on the oxygen-dependent degradation of hypoxia-inducible factors, or HIFs, which govern programs of gene expression that help cells adapt to oxygen starvation, or hypoxia. In July, Peter and his colleagues reported in Science that they’ve discovered a second system for oxygen sensing in animal cells, one so ancient that it is shared by plants. It is mediated by an enzyme, cysteamine (2-aminoethanethiol) dioxygenase, or ADO, which splits molecular oxygen (O2) and attaches each atom of the pair to an amino acid, cysteine, on its protein targets—participants in the newly discovered hypoxia pathway. This alteration allows the cysteines to be recognized by another enzyme that further modifies them, tagging the oxidized proteins for destruction. A similar system mediated by enzymes known as PCOs, which resemble ADO, operates in plant cells. While both the ADO system and the HIF system sense oxygen in similar ways, they work on different timescales. The discovery of a new cellular oxygen sensor could lead to the development of drugs for many disorders, including cancer.

This article appeared in the November 2019 issue of Ludwig Link. Click here to download a PDF (1 MB).


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