Ubiquitination

Definition

It is the covalent modification of a protein by conjugation to ubiquitin (Fig. 1). Ubiquitin is a small, 76-residue protein found in all eukaryotes. Conjugates are formed through the ligation of the C-terminus of ubiquitin to the ε-amino groups of protein lysine residues. The major, but not sole, function of ubiquitination is to target proteins for degradation by the proteasome. A large number of proteins are substrates for this regulatory pathway. Efficient targeting of proteins for degradation usually involves formation of a multiubiquitin chain on the target protein. Such chains are characterized by specific ubiquitin-ubiquitin linkages.

Fig. 1

The proteasome cycle in protein degradation. Ubiquitin is shown as a large dot, and the peptidase sites are shown as scissors. For simplicity, the 26S particle is shown with a single regulatory particle, and the 19S particle is shown without the protein mass that occupies the mouth of the wedge. Degradation of the substrate to...