Scientists Discover a Molecular Switch That Controls Life Expectancy

The insulin receptor can be controlled by the protein CHIP more efficiently when it is acting alone as opposed to when it is in a paired form, according to current research. CHIP frequently manifests as a homodimer, which is an association of two identical proteins, in conditions of cellular stress and primarily works to eliminate misfolded and faulty proteins. CHIP cleans the cell as a result. This is accomplished by the tiny protein ubiquitin being bound to misfolded proteins by CHIP in conjunction with assistance proteins.

As a result, the cell recognizes and eliminates damaged proteins. Additionally, CHIP manages the transmission of insulin receptor signal. In order to stop the activation of genes that lengthen life, CHIP attaches to the receptor and breaks it down.

Researchers from the University of Cologne have now demonstrated that CHIP may also label itself with ubiquitin, blocking the formation of its dimer, through tests involving human cells and the nematode Caenorhabditis elegans. Compared to the CHIP dimer, the CHIP monomer more efficiently controls insulin signaling. The study was carried out by the Cluster of Excellence for Cellular Stress Responses in Aging-Associated Diseases (CECAD) at the University of Cologne, and it was just released in the journal Molecular Cell.

"The condition of the cell determines whether CHIP functions alone or in pairs. According to Vishnu Balaji, the study's first author, "Under stress, there are too many misfolded proteins as well as the assistance proteins that bind to CHIP and prevent auto-ubiquitylation, the self-labeling with ubiquitin. "ChIP can target the helper proteins for destruction after successfully removing the flawed proteins. As a result, CHIP can once more function as a monomer and ubiquitylate itself.

Therefore, the monomeric and dimeric states of CHIP must be in equilibrium for the body to operate properly. It's intriguing that neurodegenerative disorders appear to disturb the monomer-dimer equilibrium of CHIP, according to Thorsten Hoppe. For instance, CHIP is altered at many locations and primarily performs as a dimer in spinocerebellar ataxias. A change to more monomers in this situation might be therapeutic.

The next step is for the researchers to determine if there are any further proteins or receptors that the CHIP monomer interacts to and controls their function. In order to create more specialized treatments in the future, researchers are particularly curious about which tissues, organs, and diseases have higher concentrations of CHIP monomers or dimers.

By UNIVERSITY OF COLOGNE