Nobel Laureate Revisiting Lecture – Sir Peter J Ratcliffe, Nobel Laureate in Physiology or Medicine 2019
Date: Thursday, June 11 at 3.30 pm
Venue: Wallenbergsalen at Nobel Forum, Karolinska Institutet, Nobels väg 1
New insights into the signalling of hypoxia in cells
Peter J Ratcliffe, Distinguished Scholar, Ludwig Institute for Cancer Research, Oxford and Group Leader, the Francis Crick Institute, London.
In human and animal cells, transcriptional responses to hypoxia are transduced by the HIF (hypoxia inducible factor) hydroxylase pathway. In this system, oxygen sensitive signals are generated by the catalytic action of a set of 2-oxoglutarate dependent dioxygenases that post-translationally hydroxylate specific prolyl residues to promote the proteolytic destruction of HIF-alpha subunits. In hypoxia this process is suppressed allowing HIF to escape destruction, and transduce an extensive transcriptional cascade. Although unprecedented as a signalling mechanism at the time, it is now clear that all eukaryotic kingdoms use enzymatic protein oxidations coupled to proteolysis to signal oxygen levels. It also has become clear that the human genome encodes many other 2-oxoglutarate dependent dioxygenases that catalyse different types of post-translational oxidation and that enzyme-catalysed protein hydroxylation is more common than previously foreseen. The lecture will discuss the extent to which these systems signal hypoxia in human cells, and the extent to which they interact with different processes contributing to physiological oxygen homeostasis.
Host: Professor Randall S. Johnson, randall.johnson@ki.se
Contact: Nobel Office, nobelforum@nobelprizemedicine.org