The 2019 #NobelPrize in Physiology or Medicine has been awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability.”
2019 Medicine Laureates William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza have identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen.
The fundamental importance of oxygen has been understood for centuries, but how cells adapt to changes in oxygen levels has long been unknown. This year’s #NobelPrize awarded work reveals the molecular mechanisms that underlie how cells adapt to variations in oxygen supply.
Oxygen sensing is central to a large number of diseases. The discoveries made by this year’s #NobelPrize laureates have fundamental importance for physiology and have paved the way for promising new strategies to fight anaemia, cancer and many other diseases.
When oxygen levels are low (hypoxia), HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes.
At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α.
The VHL protein can then recognise and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner.
Source: The Nobel Prize website
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