IRCM researchers identify a protein that controls the “guardian of the genome”

A new study published in the scientific journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) sheds new light on a well-known mechanism required for the immune response. Researchers at the IRCM, led by Tarik Möröy, PhD, identified a protein that controls the activity of the p53 tumour suppressor protein known as the “guardian of the genome”.

The researchers study the development of T cells and B cells, which are lymphocytes (or immune cells) that play a central role in protecting our body against infections by viruses, bacteria and other microbial agents.

“As these lymphocytes develop, they must learn how to recognize different pathogens in the body,” says Dr. Möröy, Director of the Hematopoiesis and Cancer research unit at the IRCM. “Part of this process involves the breaking and rearranging of the genes responsible for producing the lymphocyte receptors that recognize these pathogens. However, when a cell's genome contains too many breaks, p53 (the “guardian of the genome”) gets alerted and causes the cell to die.”

“In developing immune cells, activation of p53 must be contained to avoid their premature death,” explains Marissa Rashkovan, first author of the study and doctoral student in Dr. Möröy's laboratory. "We discovered that a protein called Miz-1 can exert such a function by controlling the activity of p53. More specifically, Miz-1 controls the way in which p53 gets alerted when a cell needs to die. In fact, without Miz-1, developing lymphocytes always activate the p53 protein and, hence, never survive."

“Our study therefore helps advance our understanding of how an efficient immune response is built in our body,” adds Dr. Möröy, who is also the IRCM's President and Scientific Director. “Our results show that, by controlling the activity of p53 and preventing premature cell death, Miz-1 ensures the survival of lymphocytes during their critical phase of development and, thereby, the proper functioning of our immune system.”

About the study

IRCM authors for the article published in PNAS include Marissa Rashkovan, Charles Vadnais, Julie Ross, Christian Kosan and Tarik Möröy (Director) from the Hematopoiesis and Cancer research unit, as well as Mathieu Gigoux and Woong-Kyung Suh (Director) from the Immune Regulation research unit. The researchers also collaborated with Wei Gu from Columbia University. The study was funded by grants from the Canadian Institutes of Health Research (CIHR), the Canada Research Chair program and the Cole Foundation.

For more information on this discovery, please refer to the article summary published online by PNAS: www.pnas.org/content/early/2014/12/02/1412107111.abstract.    

About Tarik Möröy

Tarik Möröy obtained a PhD in biochemistry from the Ludwig-Maximilians University in Munich, Germany. He is the IRCM's President and Scientific Director, Full IRCM Research Professor and Director of the Hematopoiesis and Cancer research unit. Dr. Möröy is also Full Research Professor in the Department of Microbiology, Infectiology and Immunology at the Université de Montréal, and Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) at McGill University. Dr. Möröy holds the Canada Research Chair in Hematopoiesis and Immune Cell Differentiation. For more information, visit www.ircm.qc.ca/moroy.

About the IRCM

The IRCM (www.ircm.qc.ca) is a renowned biomedical research institute located in the heart of Montréal's university district. Founded in 1967, it is currently comprised of 35 research units and four specialized research clinics (cholesterol, cystic fibrosis, diabetes and obesity, hypertension). The IRCM is affiliated with the Université de Montréal, and the IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). It also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Economy, Innovation and Export Trade (Ministère de l'Économie, de l'Innovation et des Exportations).

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For more information and to schedule an interview with Dr. Möröy, please contact:

 

Julie Langelier, Communications Officer (IRCM)

julie.langelier@ircm.qc.ca | (514) 987-5555

Lucette Thériault, Communications Director (IRCM)

lucette.theriault@ircm.qc.ca | (514) 987-5535