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 immune response. Researchers at the IRCM, led by Tarik Moroy, 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.”
Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination. Published online before print December 2, 2014, doi: 10.1073/pnas.1412107111 PNAS
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.
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.