Acidity, as during hypoxia, targets VHL (green) to the nucleous (right).
Ubiquitin tagging alters protein fates, often marking substrates for degradation. Regulation of the process occurs at the level of the ubiquitin ligases, called E3s, which facilitate the transfer of ubiquitin from a conjugating enzyme to the target protein. Several E3 proteins aggregate in the nucleolus in response to inhibitory signals. The new results show that two different E3 enzymes, MDM2 and von Hippel-Lindau tumor suppressor (VHL), become immobilized in the structure and probably bind nucleolar scaffold proteins.
In the presence of oxygen, VHL tags the hypoxia-inducible factor (HIFα), causing its degradation. The authors identified a domain within VHL that...
