Protein Ubiquitination in Eukaryotic Biology
Ubiquitin is a small protein conserved in all eukaryotes. The cell uses ubiquitin to modify many other proteins to modulate their functions. When a protein substrate is modified by a chain of multiple ubiquitin molecules, it will be targeted to the proteasome for degradation. Ubiquitin-dependent protein degradation is involved in the regulation of a large number of important proteins in the cell.
Ubiquitin has several homologous relatives, including Nedd8, SUMO, and ISG15. These ubiquitin-like proteins are also protein modifiers. Upon covalently attached to a protein in a monomer form, ubiquitin and ubiqutin-like proteins can either present a cellular signal or change the surface property, therefore, biological behavior of the target.
Ubiquitin E3 Ligases
Protein ubiquitination is tightly controlled in eukaryotic cells. It is catalyzed by a family of enzymes called ubiquitin ligases. At the end of a three-enzyme (E1-E2-E3) cascade, the ubiquitin E3 ligase mediates the transfer of a ubiquitin from the ubiquitin E2 conjugating enzyme to the protein substrate and dictates the specificity of the reaction. One particular ubiquitin ligase usually can only bind one or a limited set of protein substrates. Given the large number of proteins that are controlled by ubiquitin-dependent proteolysis, it is expected that there are hundreds of thousands of ubiquitin ligases in human cells.