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HFI-1 gene has key role in both oxygen sensing, heat shock pathway

University of Oregon researchers have found an unexpected regulatory link between cellular responses to hypoxia and heat shock. Central to the discovery is a gene known as Hypoxia-Inducible Factor-1 (HIF-1) that is critical for both normal and pathological changes, making it a potential target for both health promotion and cancer therapies.

In their study, researchers used microarray technology to observe the activity of genes found in the genome of the fruit fly (Drosophila). With it, they watched as the activity of heat shock proteins was turned on under conditions of low oxygen, or hypoxia. A microarray allows researchers to place tens of thousands of genes on 1.5-inch-square slides and study them under a microscope.

"These are proteins that were previously known to turn up under conditions of heat shock," said Eric Johnson, a professor in the UO Institute of Molecular Biology. "Now they are coming into view in hypoxia conditions as well."

When Johnson's team manipulated the genes to knock out the activity of HIF-1, the change dramatically lowered the presence of heat shock proteins. Over-activation of HIF-1 is often seen in a wide variety of cancers.

"We've found that there is more complexity to how a cell responds to a change in the environment than what we had long suspected," he said. "Instead of having a simple sensing and response process, there are sensing, calibrations, fine-tuning and responses that occur. These connections can now be targeted for therapies."

The findings of the research, which was supported by an American Cancer Society Research Scholar Grant to Johnson, appear online in advance of regular publication in the Journal of Biological Chemistry.

"This HIF-1 activity was somewhat surprising, because people in the past have often thought that these different pathways that sense environmental change have been separate entities," Johnson said. "It has been assumed that different pathways r
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Contact: Jim Barlow
jebarlow@uoregon.edu
541-346-3481
University of Oregon
25-Oct-2006


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