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Rubicon protein is key regulator of immune system, study shows

Rubicon Protein Is Key Regulator of Immune System, Study Shows
Rubicon is known to regulate the process in which a cell breaks down unwanted or damaged products.

A global team of microbiologists led by USC has identified a critical protein in the fight against bacterial and fungal infections, such as tuberculosis and ringworm, laying 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,” said Jae Jung, professor and chairman of the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of 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 Cell sister 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, such as 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 said. “It is surprising that the ‘autophagy protein’ controls two other processes.”

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

Other USC co-authors included Chul-Su Yang, Jong-Soo Lee and Mary Rodgers, postdoctoral fellows at the Keck School; students Hee Jin Kim and Chan-Ki Min; research assistant June-Yong Lee; Ambrose Jong, associate professor of pediatrics; Ebrahim Zandi, associate professor of molecular microbiology and immunology; and Chengyu Liang, assistant professor of molecular microbiology and immunology.

The research was conducted in collaboration with the College of Veterinary Medicine at Chungnam National University in Korea, the M. D. Anderson Cancer Center at The University of Texas, the School of Medicine at Boston University, the KAIST Institute for the BioCentury at the Korea Advanced Institute of Science and Technology and the Mount Sinai School of Medicine in New York. It was supported with funds from the National Research Foundation of Korea, the Hastings Foundation and The Fletcher Jones Foundation.

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Rubicon protein is key regulator of immune system, study shows

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