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Discovery in plants suggests entirely new approach to treating human cancers

BLOOMINGTON, Ind. -- For the first time, scientists from the University of Washington School of Medicine, Indiana University Bloomington and the University of Cambridge have determined how a plant hormone -- auxin -- interacts with its hormone receptor, called TIR1. Their report, on the cover of this week's issue of Nature, also may have important implications for the treatment of human disease, because TIR1 is similar to human enzymes that are known to be involved in cancer.

"Learning that auxin regulates TIR1 is a huge advance for plant biology that will probably have important implications for agriculture in the future," said IU Bloomington plant biologist Mark Estelle. "It's a bonus for us that TIR1 is related to proteins in other organisms, including humans. Some of TIR1's human relatives play a role in different human cancers, and it is possible that our work on plants will eventually lead to new cancer drugs."

Until now it was believed enzymes like TIR1, called ubiquitin ligases, could only be controlled through protein-protein interactions. Ubiquitin ligases influence growth and light response in plants, poison mitigation in yeasts and also cancerous cell division in humans.

"Although ubiquitin ligases have long been recognized as potential drug targets for treating cancers and other human diseases, it's been a bumpy road for scientists to come up with a feasible approach," said University of Washington School of Medicine pharmacologist Ning Zheng, who led the research. "The mechanism by which auxin works points out a new direction for us to develop therapeutic compounds targeting ubiquitin ligases."

The scientists extracted and purified TIR1 from the common plant model Arabidopsis. By x-raying crystals of the protein, Zheng, Estelle and colleagues determined the enzyme's three-dimensional structure -- a first for plant hormone receptors. The scientists then soaked the crystal in a solution containing auxin and
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Contact: David Bricker
brickerd@indiana.edu
812-856-9035
Indiana University
4-Apr-2007


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