Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 9
Reconstitution of human hypoxia inducible factor HIF-1 in yeast cells: a simple in vivo
system for identification of HIF-1 inhibitors.
Georgia Braliou, Emmanouel Venieris, Alkmini Kalousi and George Simos
Laboratory of Biochemistry, School of Medicine, University of Thessaly, Larissa,
Greece. E-mail: simos@med.uth.gr
Hypoxia inducible factor 1 (HIF-1) is the master regulator of the genes that are activated
under hypoxic conditions. HIF-1 is also involved in many diseases, including cancer, and is
an important target for drug development. The control of HIF-1 itself is complex and involves
many post-transcriptional events triggered by hypoxia and by various signaling and oncogenic
pathways that operate in metazoan cells. In order to study the basic function of human HIF-1
in a simple and genetically tractable in vivo system we attempted to express it in the yeast S.
cerevisiae that lacks the components of the mammalian hypoxia response pathway. We show
here that inducible expression of both human HIF-1 subunits (HIF-1alpha and ARNT) in
yeast is possible and leads to the formation of a transcriptional active heterodimer, as shown
by hypoxia response element (HRE) - dependent production of a reporter enzyme. The
activity of HIF-1 in yeast is impaired by two Hsp90 inhibitors, geldanamycin A and radicicol,
and by mutations in Hsp90 co-chaperones, suggesting that the Hsp90 chaperone system is
important for HIF-1 integrity. We conclude that the expression of human HIF-1 in yeast
provides a model system for both functional studies and identification of compounds that can
act as direct HIF-1 inhibitors.
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