A new discovery about plant proteins may lead to developments in cancer treatments, UW researchers report.

In collaboration with scientists from Indiana University and the University of Cambridge, UW researchers have identified an important plant protein, TIR1, as the receptor for auxin, a hormone that regulates growth and development.

The discovery shows TIR1 relates to a human enzyme found 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,” Indiana University’s Dr. Mark Estelle of told Nature magazine.

In 2005, Estelle had identified the plant protein TIR1. He requested collaboration with UW researchers Ning Zheng and Xu Tan to help the project by using X-ray crystallography to produce 3-D images of TIR1 with auxin.

“After its identification, the immediate question is how auxin is sensed by this protein and how this hormone in turn regulates plants,” said Zheng, an associate professor of pharmacology.

Researchers extracted and purified TIR1 from the common plant arabidopsis before mapping it using X-ray crystallography.

TIR1 was soaked in crystal solution containing auxin to find binding sites. A peptide was added to observe binding behavior. The structure was found to be tightly bound in the presence of auxin. Without auxin, TIR1 did not bind with the peptide as tightly, showing auxin’s role as a “molecular glue,” researchers said.

“In the past, all efforts have focused on looking for ubiquitin ligase inhibitors,” Zheng said. “However, auxin teaches that the opposite direction might be more feasible. It might be easier to come up with ubiquitin ligase enhancers.”

The completion of this research project opens the door to development of new therapeutic compounds for human diseases such as cancer.

“The results will have a great impact on plant biology as well as drug development for human diseases, such as cancer and neurodegenerative diseases,” said Tan, UW graduate student of pharmacology.

These newly developed compounds would target the malfunctioning ubiquitin ligases. In plants, ubiquitin ligases influence growth and light responses. Until now, it was believed that the interaction could only be controlled by protein-protein interaction.

“Since ubiquitin ligases were found, scientists were looking for ways of manipulating them by small molecules, hoping that these small molecules can be developed into therapeutics,” Zheng said. “The plant hormone auxin is a naturally occurring small molecule that controls the activity of TIR1, an ubiquitin ligase; we think we can now follow the principle of how auxin works to search for new classes of compounds.”

Colon and breast cancers are caused by defective interaction between ubiquitin ligases and their substrate polypeptides. This discovery may give organic chemists the opportunity to synthesize small molecules like auxin to produce a new type of cancer drug.

“If this new discovery does fulfill the potential to develop an effective cancer drug, the American Cancer Society would happily to fund, promote or help in any way,” said Kristin Ratigan, an American Cancer Society representative.

Reach reporter Victoria Lee at news@thedaily.washington.edu.