Enzyme ATE1 is Involved in Cellular Stress Response

How a previously unknown enzyme functions in the cell has been revealed by a new article published in Nature Communications. Several diseases are linked to chronic cellular stress, and Aaron T. Smith and colleagues at UMBC revealed that this enzyme is involved in the cellular stress response. Understanding how this enzyme works and how it is controlled could lead to the identification of new treatment targets for these disorders.

Enzymes Help To Get Rid of Disease-Causing Proteins

The enzyme is known as ATE1, and it is a member of the arginyl-tRNA transferase family. These enzymes add arginine (an amino acid) to proteins, which frequently marks them for degradation in the cell. It is critical to destroy misfolded proteins, which are frequently caused by cellular stress, to avoid such proteins from interfering with cellular function. A buildup of defective proteins in the body can create major difficulties, leading to diseases such as Alzheimer's or cancer, thus being able to get rid of these proteins efficiently is critical to long-term health.

Implications of ATE1 in Modulating Cellular Stress

The current study shows that ATE1 attaches to iron-sulfur ion clusters and that the enzyme's activity rises two to thrice when linked to one of these iron-sulfur clusters. Furthermore, when the researchers inhibited the cells' ability to form clusters, ATE1 activity dropped drastically. They also discovered that ATE1 is particularly sensitive to oxygen, which they believe is related to its involvement in modulating the cell's stress response via oxidative stress. “We were very excited about that because it has lots of very tantalizing downstream implications, particularly related to the enzyme’s role in disease,” says Smith, associate professor of chemistry and biochemistry.

Smith's lab initially worked with yeast proteins, but they discovered that the mouse form of ATE1 functions similarly. That’s important, Smith explains. “Since the yeast protein and the mouse protein behave the same way,” he says, “there’s reason to believe, that because the human protein is quite similar to the mouse protein, it likely behaves the same way as well.”

Smith and then-graduate student Verna Van, Ph.D. '22, biochemistry and molecular biology, had been striving for quite some time to induce ATE1 to interact with heme, a molecule that contains iron and is required to bind oxygen in the blood, to corroborate the results of another group. Smith confesses that it was not working and that they were becoming frustrated. Nevertheless, when preparing a lecture on proteins that interact with clusters of metal and sulfur atoms, Smith noticed that the proteins he was about to cover with his students resembled ATE1.

The fact that the enzyme binds the clusters at all was interesting and new, “but then we also asked if that’s affecting the enzyme’s ability to do what it does,” Smith says.

Source-Medindia