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What Is the Ubiquitin System?

By H. Colledge
Updated May 17, 2024
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Ubiquitin is a type of protein found in eukaryotic cells. Eukaryotic cells have a cell nucleus and are found in humans, animals, plants and fungi. Inside cells, proteins are continually synthesized and broken down, or degraded, and the ubiquitin system helps regulate this protein turnover. Ubiquitin attaches itself to those proteins which are to be degraded, effectively tagging them. Then the proteins are taken to a structure called a proteasome where degradation takes place.

Proteins are made of units called amino acids, and 76 amino acids make up the small ubiquitin protein. The sequence of these amino acids does not change very much in different organisms, so yeast ubiquitin and human ubiquitin only contain around three sequence differences. Ubiquitin gets its name from the word ubiquitous, which refers to something that is found everywhere. In keeping with its name, ubiquitin is not limited to one part of the cell but is present everywhere. The ubiquitin system is involved in many cellular processes where protein modification occurs, including the growth, division and death of cells, and the copying and repair of DNA.

Before the ubiquitin system can begin to work, ubiquitin must be activated. This step requires energy in the form of adenosine triphosphate (ATP), a structure which carries chemical energy inside the cell. The energy is needed to enable an enzyme called E1 to activate ubiquitin.

Next, two more ubiquitin system enzymes, known as E2 and E3, act together to attach ubiquitin to the target protein. It is thought that E3 also helps to identify the protein, and one or more ubiquitin molecules may then be attached to it. The signal that marks a protein for recognition by the ubiquitin system is not known, although scientists think certain amino acids may be responsible, some of which may remain hidden unless the protein unfolds or takes part in a reaction.

Finally, the protein with its ubiquitin tag is transferred to a proteasome to be degraded. Some scientists think that ubiquitin helps to keep the protein attached to the proteasome while degradation takes place, preventing it from breaking away too early. Proteasomes are cylindrical protein-degrading machines which consist of a stack of rings. The rings at each end of the cylinder are inactive while the central rings are active and enclose a chamber in which proteins are broken down. Caps on both ends of the cylinder attach to ubiquitin and direct proteins into the chamber for degradation.

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