deformed protein folder (chaperone)'s influence

In molecular biology, chaperones are a class of proteins that help regulate how other proteins fold. Folding is an important step in the manufacturing process for proteins. When they don't fold the way they're supposed to, it can lead to the development of diseases such as cancer.

Researchers at the Sloan Kettering Institute have uncovered important findings about what causes chaperones to malfunction as well as a way to fix them when they go awry. 

"Our earlier work showed that defects in chaperones could lead to widespread changes in cells, but no one knew exactly how it happened,"

The research focused on a chaperone called GRP94, which plays an important role in regulating how cells respond to stress. Stress in cells is a common sign of disease, especially those related to aging, such as cancer and Alzheimer's. Dr. Chiosis has studied the role of chaperones and stress in both of these disorders for many years.

They found that when GRP94 undergoes a process called glycosylation, in which a sugar molecule is added, it completely changes the way that chaperone behaves.

When GRP94 undergoes this change, it moves to a different part of the cell. Normally, it's found in the endoplasmic reticulum, where proteins are made and folded. But after the sugar is added, it moves to the part of the cell called the plasma membrane. This leads to widespread dysfunction of proteins and a more aggressive cancer.

 

reference

Pengrong Yan et al, Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.107840