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Archive - Sep 22, 2013

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Researchers ID Protein That Regulates Cellular Trafficking, Has Potential for Anti-Cancer Therapy

Molecular microbiologists at the University of Southern California (USC) have uncovered intricate regulatory mechanisms within the cell that could lead to novel therapeutics for the treatment of cancer and other diseases. Their findings, which have long-standing significance in the basic understanding of cell biology, were published online on Septermber 22, 2013 in the journal Nature Cell Biology. "Our research reveals a new regulatory mechanism that coordinates two distinct intracellular processes that are critical to cellular homeostasis and disease development," said Chengyu Liang, M.D., Ph.D., a member of the USC Norris Comprehensive Cancer Center and principal investigator of the study. The endoplasmic reticulum (ER) and Golgi apparatus are cellular organelles in eurkaryotic organisms where proteins are synthesized and packaged for secretion through the body. The trafficking of proteins between the ER and Golgi must be tightly modulated to maintain the health of the cell and prevent diseases like cancer from taking hold. "Interest in the role of ER-Golgi network during cancer cell death has been gaining momentum," said Shanshan He, Ph.D., research associate at the Keck School of Medicine of USC and one of the study's first authors. "In this study, we identified a novel regulatory factor for the Golgi-ER retrograde transport and a new mechanistic connection between the physiological trafficking and the autophagic transportation of cellular material." The researchers discovered that the UV irradiation resistance-associated gene protein (UVRAG) (see image), which has been implicated in the suppression of colon and breast cancer, coordinates trafficking of proteins between the ER and Golgi apparatus and also autophagy, the natural process of breaking down cellular components.

Discovery of Propofol Binding Site May Aid Additional Anesthetic Discoveries

Researchers at the Washington University School of Medicine in St. Louis and Imperial College London have identified the site where the widely used anesthetic drug propofol binds to receptors in the brain to sedate patients during surgery. Until now, it has not been clear how propofol connects with brain cells to induce anesthesia. The researchers believe the findings, reported online on September 22, 2013 in the journal Nature Chemical Biology, eventually will lead to the development of more effective anesthetics with fewer side effects. "For many years, the mechanisms by which anesthetics act have remained elusive," explained co-principal investigator Alex S. Evers, M.D., the Henry E. Mallinckrodt Professor and head of the Department of Anesthesiology at Washington University. "We knew that intravenous anesthetics, like propofol, act on an important receptor on brain cells called the GABAA receptor, but we didn't really know exactly where they bound to that receptor." Propofol is a short-acting anesthetic often used in patients having surgery. It wears off quickly and is less likely to cause nausea than many other anesthetics. But the drug isn't risk-free. Its potentially dangerous side effects include lowering blood pressure and interfering with breathing. In an attempt to understand how propofol induces anesthesia during surgery, scientists have tried to identify its binding site within the gamma-aminobutyric acid type A (GABAA) receptor on brain cells. Activating these receptors — with propofol, for example — depresses a cell's activity. Researchers have altered the amino acids that make up the GABAA receptor in attempts to find propofol's binding site, but Dr. Evers said those methods couldn't identify the precise site with certainty.

Scientists ID Potential On/Off Switch for Deadly Brain Tumor Cells

Researchers at the University of Texas (UT) Southwestern Medical Center have identified a cellular switch that potentially can be turned off and on to slow down, and eventually inhibit the growth of the most commonly diagnosed and aggressive malignant brain tumor. Findings of their investigation show that the protein RIP1 acts as a mediator of brain tumor cell survival, either protecting or destroying cells. Researchers believe that the protein, found in most glioblastomas, can be targeted to develop a drug treatment for these highly malignant brain tumors. The study was published online on August 22, 2013 in Cell Reports. "Our study identifies a new mechanism involving RIP1 that regulates cell division and death in glioblastomas," said senior author Dr. Amyn Habib, associate professor of neurology and neurotherapeutics at UT Southwestern, and staff neurologist at the VA North Texas Health Care System. "For individuals with glioblastomas, this finding identified a target for the development of a drug treatment option that currently does not exist." In the study, researchers used animal models to examine the interactions of the cell receptor EGFRvIII and RIP1. Both are used to activate NFκB, a family of proteins that is important to the growth of cancerous tumor cells. When RIP1 is switched off in the experimental model, NFκB and the signaling that promotes tumor growth is also inhibited. Furthermore, the findings show that RIP1 can be activated to divert cancer cells into a death mode so that they self-destruct. According to the American Cancer Society, about 30 percent of brain tumors are gliomas, a fast-growing, treatment-resistant type of tumor that includes glioblastomas, astrocytomas, oligodendrogliomas, and ependymomas.