Cells control their responses to the presence or absence of oxygen by an elegant system of checks and balances. Recent structural studies clarify some high-impact findings in hypoxia research, lending insight into the dynamic nature of HIF-1a , the hypoxia-induced transcription factor. This infamous molecule, when unchecked, turns on genes that enhance tumor growth. Some say these three studies,1-3 two of which are highlighted by the Faculty of 1000,1,2 offer new angiogenesis-promotion and inhibition targets. But, whether drug developers will react may rest on new knowledge about the nature of unfolded proteins.
Regardless, the molecular story is solidifying. "We always say, 'Crystal structure makes things crystal clear,'" says Yigong Shi, associate professor of molecular biology at Princeton University and an F1000 faculty member. Shi's former postdoctoral adviser, Nikola Pavletich, captured the crystal structure of HIF-1a bound to the Von Hippel-Lindau protein (pVHL), a tumor suppressor. pVHL ubiquinylates HIF-1a , targeting ...
