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Up-Regulation of Hypoxia-inducible Factor-1 Is Not Sufficient for Hypoxic/Anoxic p53 Induction¹

Institute of Physiology, University of Zürich-Irchel, CH-8057 Zürich, Switzerland

Oxygen-deprived regions of a solid tumor can induce tumor suppressor p53 expression and hence select for p53-mutant tumor cells with diminished apoptotic potential. It has been proposed that the hypoxia-inducible factor-1 (HIF-1) subunit binds to p53 and protects it from proteasomal degradation. However, we found that hypoxic conditions that strongly induce HIF-1-dependent endogenous gene expression as well as HIF-1 protein neither induce p53-dependent gene expression nor p53 protein. The iron chelator deferoxamine induced both HIF-1 and p53, but p53 up-regulation could still be detected in HIF-1-deficient cells, suggesting that mechanisms other than HIF-1 activation contribute to oxygen-regulated p53 induction.

¹ Supported by the Swiss National Science Foundation (31-47111.96). R. H. W. is a recipient of the Sondermassnahmen des Bundes zur Förderung des akademischen Nachwuchses.

² To whom requests for reprints should be addressed, at Physiologisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Phone: (41) 1 6355051; Fax: (41) 1 6356814; E-mail: labbauer@physiol.unizh.ch.

Received 9/ 8/98. Accepted 10/28/98.

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