Discovering HIF Regulation

In the complicated, occasionally counter-intuitive world of signal transduction pathways, sometimes events turn out to be much simpler than first supposed.

Eugene Russo
Apr 20, 2003

APPETITE FOR DESTRUCTION: Schematic representation shows the 15-residue portion of the HIF-1a destruction sequence, which is bound to the B domain of pVHL in the pVHL-ElonginB-ElonginC complex.
Reference Reprinted with permission from science, 296:1886-9, 2002

In the complicated, occasionally counter-intuitive world of signal transduction pathways, sometimes events turn out to be much simpler than first supposed. Such is the case with an important oxygen- sensing pathway, the essential features of which investigators Bill Kaelin at Dana-Farber Cancer Institute and Peter Ratcliffe at the University of Oxford independently describe in these Hot Papers.1,2

Understanding how cells sense oxygen has potentially important implications for research in cancer, diabetes, and many ischemic diseases. The appropriate delivery of oxygen by the lungs, heart, blood, circulation, and blood vessels to all cells is a delicate operation: Too little oxygen impairs metabolism; too much oxygen is toxic.

The search for the oxygen-sensing...