Team from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences (CAS) uncover a protein quality control mechanism that removes misfolded membrane proteins.
Accumulation of misfolded membrane proteins can disrupt the normal functioning of the cell. Additionally, long term aggregates of these proteins can be toxic to the human body which can result in various diseases such as neurodegeneration.
A group of researchers recently discovered, “re-ubiquitination”, a protein quality control mechanism shown to promote elimination of misfolded membrane proteins, and reduce the time these proteins are present in cells. This process will inevitably assist in reducing the formation of toxic protein aggregates.
RNF126 is an E3 ubiquitin ligase that adds a small protein known as ubiquitin to the misfolded protein, thereby targeting them for degradation by proteasomes. Results from the study showed that RNF126-mediated re-ubiquitination is key for normal cell physiology. Also, clearing of misfolded proteins in cells through the ubiquitin-proteasome system will prevent formation of pathological aggregates that are damaging to the cells.
Absence of re-ubiquitination could lead to delayed targeting of misfolded proteins by proteasomes, increasing the risk of protein aggregation and cellular stress, which gradually results in disease.
In addition, the function of RNF126 as a re-ubiquitinase might be required for rapid proliferation of certain cancer cells, making it a potential therapeutic target.
This work has been published online in July 8, 2020 in Molecular Cell, and it was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, and the Shanghai Municipal Science and Technology Major Project. [APBN]