Role of newly identified pathway in disease progression published in Cell
SOUTH PLAINFIELD, NJ April 30, 2004 PTC Therapeutics, Inc. (PTC), today announced the first identification in humans of an enzyme complex underlying the metabolism of tRNA and mRNA, two integral components of cell proliferation. This research, published in the April 30th issue of the scientific journal Cell, provides compelling evidence for the existence of a new biochemical pathway that may lead to the discovery of new drugs for the treatment of proliferative disorders. Such disorders are characterized by rapidly and uncontrollably dividing cells and include malignancies such as leukemia, lymphoma, multiple myeloma, solid tumors, and inflammatory diseases such as psoriasis.
"The recent work by PTC's researchers is extraordinary in that it creates a physical, and possibly regulatory link between the pathways that create RNA messengers and those that create the translational machinery for turning those messages into proteins," said Dr. David R. Engelke, Director of the Program of Biomedical Sciences at the University of Michigan. "Researchers have always treated these processes as entirely separate sets of reactions. It is now clear that they are intertwined, whether investigating fundamental mechanisms in normal cells or searching for drug targets to identify novel therapeutics."
Dr. Christopher R. Trotta, Senior Scientist at PTC and Principal Investigator in this work comments: "Overexpression of tRNA and mRNA is a key factor in the deregulation of translation that allows cancer cells to grow uncontrollably. This newly discovered biochemical pathway represents an Achilles' Heel of tumor cell growth and opens a new door in the development of therapeutics."
(more) Expression of genetic information is an ordered, multi-step process that proceeds from DNA to RNA to protein. Deregulation of any step in this process can lead to a number of diseases. Messenger RNA and transfer RNA are required for the production of proteins within a cell. The amount of each of these types of RNA is tightly controlled in normal cells. Proliferative diseases result in overproduction of these two types of RNA, allowing cells to grow uncontrollably. In the course of investigations aimed at understanding gene expression in human cells, PTC scientists discovered an enzyme complex that provides evidence for a novel biochemical pathway that controls the maturation of both tRNA and mRNA. Inhibitors that target the RNA processing events carried out by this enzyme complex create new opportunities for therapeutic intervention. PTC has filed worldwide patent applications to secure its ownership rights in all aspects of this discovery.
"This important finding adds to our repertoire of post-transcriptional mechanisms of RNA processing and illustrates our expertise in RNA biology. We are excited by the discovery of this novel enzyme complex and its implications in the identification of therapeutics that target novel mechanisms of post-transcriptional control processes," said Stuart W. Peltz, Ph.D., President and CEO of PTC.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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