Cancer is in large part a disease related to aging – that is, the frequency of the onset of cancer increases dramatically with age. A major challenge for scientists is to understand how, with time, normal cells "go haywire" and become cancerous cells. Paul Schimmel, Ph.D., a world-renowned biochemist and molecular biologist at The Scripps Research Institute, has now discovered a new mechanism of how defective and abnormal proteins are formed and may initiate cancer in aging cells-which could lead to novel strategies for treating and preventing cancer in the aging population.
Proteins, when in their correct forms, are key molecules that keep our bodies in their normal, healthy state; therefore, even small defects that are mistakenly built into proteins could cause profound problems. Dr. Schimmel has devoted his 40+-year career to research on tRNA synthetases, enzymes which build all proteins from the genetic code (mRNA) and also correct any errors in proteins as they are made. He proposes that if tRNA synthetases become defective themselves, then they are unable to correct the errors occurring in proteins as they are constructed. These errors in protein production accumulate, or occur more often, as a cell ages, and some defective proteins eventually can lead to the activation of genes that cause cancer.
Using their unique tumor model system, the Schimmel team is able to introduce genes for tRNA synthetases that are defective in their normal editing function. This model allows the scientists to learn how the construction and accumulation of proteins with errors, over time, relates to cancer initiation in cells. Verification of Dr. Schimmel's mechanism-that defective tRNA synthetases can initiate cancer-may lead to the development of novel strategies for treating and preventing cancer in aging individuals. The potential is there for fully functional tRNA synthetases to become therapeutic agents, or for the defective ones to become targets for drugs, yielding many opportunities for cancer intervention and cancer prevention.