Protein Research Advances Parkinson’s and Breast Cancer Treatment

Oregon Health & Science University study could one day lead to treatments that prevent or treat diseases and infections linked to a protein found in all human cells.

The protein ubiquitin is transformed during a bacterial infection, according to a study published today in the journal Molecular Cell. The study describes the processes necessary to synthesize lysine 6 polyubiquitin, a type of protein in which a lengthy chain of ubiquitin monomers is linked by the amino acid lysine. This type of ubiquitin aids cell communication by transmitting a chemical message — communication that is still poorly understood.

Previous research has connected this type of ubiquitin to the development of Parkinson’s disease and breast cancer. However, it is unclear how lysine 6 polyubiquitin is generated or how it is related in disease.

To investigate this, OHSU researchers focused on pathogenic bacteria and how they modify lysine 6 polyubiquitin during infection. The researchers extracted enzymes utilized by E. coli and Salmonella to cause food poisoning and other ailments and studied how they interacted with ubiquitin.

The researchers discovered that one specific enzyme was essential for the formation of lysine 6 polyubiquitin.

Previously, the same scientists discovered that a separate enzyme from a different illness-causing bacteria, Legionella pneumophila, which causes a kind of pneumonia known as Legionnaires’ disease, actively tears apart the same molecule during infection.

This means that during infection, various enzymes have varied effects on the same lysine 6 polyubiquitin.

“Knowing how lysine 6 polyubiquitin is regulated is an important first step,” said senior researcher Jonathan Pruneda, Ph.D., an assistant professor of molecular microbiology and immunology at OHSU. “We’ll use this knowledge as a foundation for future research, including looking into how bacteria use ubiquitin to infect cells.”

“One day, I hope we can harness this research to develop new ways to prevent and treat infections and disease.”

Pruneda and colleagues are actively investigating the role of lysine 6 polyubiquitin regulation in Parkinson’s disease and breast cancer.

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