Regulator protein plays double duty

USC (US) — Microbiologists have identified a critical protein in the fight against bacterial and fungal infections like tuberculosis and ringworm.

The findings lay the groundwork for scientists to develop target-specific drugs that have fewer side effects.

“We have found a single protein that controls three major immune processes, but each of those processes are functionally and genetically separable,” says Jae Jung, professor of molecular microbiology and immunology at the University of Southern California (USC).


“That means if we block one process, the protein is still able to mediate the other two. This is important for drug makers. Using small molecules, we may be able to modulate specific interactions and minimize side effects.”

Jung is the senior author of a pair of studies detailing the discovery in the March 15 issue of the journal Cell Host & Microbe.

Discovered in 2009, the protein Rubicon is known to regulate autophagy, the process in which a cell breaks down unwanted or damaged products. Perhaps the most well known mechanism of autophagy involves the formation of a membrane around a target in the cell, separating it from the rest of the cell before the contents of the vesicle decomposes.

In the current study, Jung and colleagues observed that Rubicon also activates phagocytosis, the process in which special white blood cells called phagocytes ingest harmful particles like bacteria and dying cells.

It appears that in the presence of bacteria, Rubicon binds to specific enzymes that alert the phagocytes to jump into action. The researchers found that the protein acts in the opposite way in fungal infections by acting like a physiological brake to the body’s natural anti-fungal immune response.

“Immunology is so dynamic,” Jung says. “It is surprising that the ‘autophagy protein’ controls two other processes.”

The new information may play a key role in drug development, Jung says. How and why Rubicon acts the way it does are yet to be determined.

Additional researchers from USC contributed to the study, as well as collaborators at the College of Veterinary Medicine of Chungnam National University in Korea, the University of Texas M.D. Anderson Cancer Center, Boston University School of Medicine, KAIST Institute for the Biocentury of the Korea Advanced Institute of Science and Technology in Korea, and Mount Sinai School of Medicine in New York.

The research was supported with funds from the National Research Foundation of Korea, Hastings Foundation, and the Fletcher Jones Foundation.

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