Scientific Publications

NEW CELL MECHANISMS OF STRESS RELIEF

A new study published in Cell Reports by researchers from the ICGEB China Regional Research Centre has identified a new protective measure against endoplasmic reticulum (ER) stress.

The endoplasmic reticulum (ER) is a cell organelle controlling protein synthesis, trafficking, and folding, which is the mechanism used by proteins to acquire their functional structure.

The published findings show that the decrease in SRP14 protein concentration, accompanied by reduced transfer of proteins in the endoplasmic reticulum, is a new protective measure against ER stress.

The ER also stores misfolded or unfolded proteins, which accumulate within the organelle to undergo correct folding. However, too much protein accumulation causes ER stress, a cell state found in many pathologies, like cancer, type II diabetes, and neurodegenerative diseases.

Cells react to ER stress by triggering a protective response called "Unfolded Protein Response" (UPR). When protein accumulation in the ER is too high, UPR factors reduce new protein synthesis, enhance misfolded/unfolded protein degradation, and favor appropriate protein folding, to relieve ER overload.

On 23 July, the research group of Yili Yang, from the ICGEB China Regional Research Centre, published a new study in Cell Reports showing that SRP14 protein concentration decreases upon ER stress. This decrease is associated with reduced import of newly synthesized proteins in the organelle.

While it was already known that cells alleviate ER stress via the mechanisms described above, a reduction in ER protein import as an additional protective measure was not previously explored. The study by Yang and co-workers shows that, upon ER stress, two UPR factors (PERK and eIF2α) are activated to favor SRP14 concentration decrease eventually. Specifically, SRP14 is degraded by the ubiquitin/proteasome, the cell system in charge of protein disposal. The reduction in SRP14 concentration correlates with the attenuated import of newly synthesized proteins in the ER. This means less protein transfer, less accumulation inside the organelle, and less ER stress.