Compared to the dual state, CHIP can control insulin receptors more effectively when acting alone.
A single protein can control aging signals more effectively than a group.
According to recent research, CHIP can control insulin receptors more effectively when acting alone than when acting in tandem. During cellular stress, CHIP often occurs as a homodimer — a conjugation of two identical proteins — and serves primarily to destroy defective and malfunctioning proteins. Thus, CHIP cleans the cell. To do this, CHIP connects a chain of the small protein ubiquitin with the helper proteins to the denatured proteins.
As a result, the cell recognizes and eliminates defective proteins. In addition, CHIP controls insulin receptor signaling. CHIP binds to and degrades receptors, preventing activation of life-prolonging gene products.
researchers out University of Cologne Experiments with human cells and the nematode Caenorhabditis elegans have now shown that CHIP can also label itself as ubiquitin and thus prevent the formation of its dimers. The CHIP monomer regulates insulin signaling more effectively than dimers. The research was conducted by the University of Cologne’s Cellular Stress Response in Age-Related Disorders (CECAD) Excellence Group and was recently published in the journal. molecular cell.
Whether CHIP works alone or in a pair depends on the state of the cell. Under stress, there are too many denatured proteins, as well as helper proteins that bind to CHIP and prevent its ubiquitylation, which is self-tagging with ubiquitin,” said Vishnu Balaji, first author of the study, “following CHIP successfully removes the defective proteins, it can hydrolyzed proteins can also be identified. This allows CHIP to be ubiquitous and function as a monomer once more,” he explained.
So for the body to function properly, there must be a balance between the unilateral and dual CHIP states. “Interestingly, the CHIP monomer-dimer balance seems to be disrupted in neurodegenerative diseases,” says Thorsten Hoppe. For example, in spinocerebellar ataxias, several CHIP sites are mutated and they mostly function as diploids. Here, switching to more monomers would be a possible therapeutic approach.”
In the next step, the scientists want to know whether there are other proteins or receptors to which the CHIP monomer binds and thus regulates its function. Researchers are also interested in which tissues, organs and diseases CHIP monomers or dimers are more prevalent in order to be able to develop more targeted therapies in the future.
Reference: “A Bi-Monomer Switch Controlling Chip-Dependent Substrate Diffusion and Processing” by Vishnu Balaji, Leonie Muller, Robin Lorenz, Eva Keefe, William H. Camacho, Wojciech Bokrizo, and Thorsten Hobe, August 25, 2022, Available here . molecular cell.
DOI: 10.1016/j.molcel.2022.08.003
