Researchers at the IRCM, led by geneticist Dr. Jacques Drouin, recently defined the interaction between two essential proteins that control inflammation. This important breakthrough will be published in tomorrow's print edition of the scientific journal Molecular Cell.
IRCM scientists study glucocorticoids, a class of steroid hormones that suppress the immune system and reduce inflammation. They are used in medicine to treat diseases such as allergies, asthma, and autoimmune diseases.
"In molecular biology and genetics, proteins known as transcription factors bind to DNA in order to control the expression (or transcription) of genetic information," explains Dr. Drouin, Director of the Molecular Genetics research unit at the IRCM. "Our work defined the genome-wide interaction between two transcription factors: Stat3 and the glucocorticoid receptor (GR)."
While Stat3 acts on pro-inflammatory gene targets, glucocorticoids are widely used for their anti-inflammatory properties and their receptor, GR, interacts with Stat3 to control these actions. GR can be found in almost every cell in the body and regulates genes that control development, metabolism, and inflammatory and immune response.
Transcription factors can control the flow of information alone or along with other proteins, either by promoting (as an activator) or blocking (as a repressor) the recruitment of enzymes required for the expression of specific genes. Transcription factors can bind directly to DNA or attach themselves to another DNA-bound protein.
"In some cases, the proteins will behave differently depending on how they are connected to a DNA sequence," says David Langlais, former doctoral student in Dr. Drouin's laboratory and first author of the article. "We were interested in understanding why some transcription factors could act as activators when bound directly to DNA, but act as repressors if they are recruited by another protein. The molecular basis for this dual action remained unclear until now."
Jacques Drouin's research is funded by the Canadian Institutes for Health Research (CIHR). Catherine Couture and Aurélio Balsalobre, both researchers in Dr. Drouin's laboratory, also contributed to this research project.
For more information on this discovery, please refer to the article summary published online by Molecular Cell: http://www.cell.com/molecular-cell/abstract/S1097-2765(12)00343-7.
About Dr. Jacques Drouin
Jacques Drouin obtained his Doctor of Science in Physiology from the Université Laval. He is IRCM Research Professor and Director of the Molecular Genetics research unit. Dr. Drouin is a professor in the Department of Biochemistry at the Université de Montréal. He is also associate member of the Department of Medicine (Division of Experimental Medicine), adjunct professor of the Department of Anatomy and Cell Biology, and adjunct member of the Department of Biochemistry at McGill University. In addition, he is an elected member of the Academy of Sciences of the Royal Society of Canada.
About the Institut de recherches cliniques de Montréal (IRCM)
Founded in 1967, the IRCM (www.ircm.qc.ca) is currently comprised of 36 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.
Journal
Molecular Cell