According to recent research, the protein CHIP can control the insulin receptor more effectively while acting alone than when in a paired state. In cellular stress situations, CHIP often appears as a homodimer – an association of two identical proteins – and mainly functions to destroy misfolded and defective proteins. CHIP thus cleanses the cell. In order to do this, CHIP works with helper proteins to bind a chain of the small protein ubiquitin to misfolded proteins.

As a result, the cell detects and gets rid of defective proteins. Furthermore, CHIP controls insulin receptor signal transduction. CHIP binds to the receptor and degrades it, preventing the activation of life-extending gene products. [1]

Figure 1. Scientists discover a molecular switch that controls life expectancy

Figure 1 shows researchers at the University of Cologne have now shown in tests with human cells and the nematode Caenorhabditis elegans that CHIP can also mark itself with ubiquitin and thus prevent the formation of its dimer. The CHIP monomer regulates insulin signaling more effectively than the CHIP dimer. The research was conducted by the University of Cologne’s Cluster of Excellence on Cellular Stress Responses in Age-Related Diseases (CECAD) and was recently published in the journal molecular cell. [2]

“Whether CHIP works alone or as a pair depends on the state of the cell. Under stress, there are too many misfolded proteins as well as the helper proteins that bind to CHIP and prevent auto-ubiquitylation, the self-labeling with ubiquitin,’ said Vishnu Balaji, first author of the study. [3]

‘In spinocerebellar ataxias, for example, different sites of CHIP are mutated, and it functions predominantly as a dimer. Here, a shift to more monomers would be a possible therapeutic approach.’ In the next step, the scientists want to find out whether there are other proteins or receptors to which the CHIP monomer binds, and thus regulates their function. The researchers are also interested in finding out in which tissues and organs and in which diseases CHIP monomers or dimers occur in greater numbers, in order to be able to develop more targeted therapies in the future. [4]

References:

1. https://scitechdaily.com/scientists-discover-a-molecular-switch-that-controls-life-expectancy/
2. https://localtoday.news/us/scientists-discover-a-molecular-switch-that-controls-life-expectancy-89012.html
3. https://interestingengineering.com/science/life-expectancy-molecular-switch-long
4. https://www.innovations-report.com/life-sciences/molecular-switch-controls-life-expectancy/

Cite this article:

Thanusri swetha J (2022), Scientists discover a molecular switch that controls life expectancy, Anatechmaz, pp. 410