A single protein can control aging signals more effectively than in a group. 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 associa
Compared to a paired state, the protein CHIP can control the insulin receptor more effectively when acting alone.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.
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.have now shown via tests using human cells and the nematode Caenorhabditis elegans that CHIP can also label itself with ubiquitin, preventing the formation of its dimer. The CHIP monomer regulates insulin signaling more effectively than the CHIP dimer.
Thus, for the body to function smoothly, there must be a balance between the monomeric and dimeric states of CHIP. “It’s interesting that the monomer-dimer balance of CHIP seems to be disrupted in neurodegenerative diseases,” said Thorsten Hoppe. “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.
Reference: “A dimer-monomer switch controls CHIP-dependent substrate ubiquitylation and processing” by Vishnu Balaji, Leonie Müller, Robin Lorenz, Éva Kevei, William H. Zhang, Ulises Santiago, Jan Gebauer, Ernesto Llamas, David Vilchez, Carlos J. Camacho, Wojciech Pokrzywa and Thorsten Hoppe, 25 August 2022,
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