세포 스트레스로 인한 리보솜 충돌에 따른 cell fate

When cells experience a high level of stress—for example, when they are exposed to too much UV light—ribosomes inside the cell collide and get into traffic jams. Now, Johns Hopkins scientists have found a protein that recognizes this traffic problem and pushes the cell down a path toward cell suicide.

Molecular biologist Rachel Green, Ph.D., and her team have long been studying how cells recognize problems within their coding information and how this recognition relies on cellular structure called the ribosome. These problems can arise from errors encoded in the genome or from environmental damage to the cell.

The ribosome travels along a piece of genetic material called messenger RNA (mRNA). The ribosome's job is to decode the mRNA to provide a set of instructions for making a protein. When cell stress increases, and mRNAs are damaged, ribosomes can't travel down the mRNA highway, and they tend to collide with each other like molecular bumper cars. Since these ribosomes fail to reach the end of the mRNA, they produce incomplete proteins.

"Incomplete proteins aggregate and cause diseases," "The cell needs to stop incomplete proteins from being produced and aggregating."

Green and her team aimed to find out how cells assess traffic conditions and spot these ribosomal collisions. So, they added an antibiotic that blocks ribosome movement to mammalian cells cultured in the laboratory.

The scientists found no problems with the traffic flow of ribosomes in untreated cells. With a high dose of the antibiotic, they found that ribosomes simply stopped moving all together. However, when the scientists treated the cells with an intermediate dose of the antibiotic, they saw widespread ribosome collisions in the cell and to their surprise, activation of proteins involved in both the life-promoting integrated stress response and the death-promoting ribotoxic stress response.

ZAK, which is part of a family of proteins called MAP3K. ZAK binds to colliding ribosomes and is itself activated.

 

cell은 그림을 잘 그려줘서 참 좋다.

 

reference

Colin Chih-Chien Wu et al. Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate, Cell (2020). DOI: 10.1016/j.cell.2020.06.006