Ubiquitination
From Biomatics.org
Ubiquitin is a very conserved small regulatory protein that is ubiquitous in eukaryotes. Ubiquitination (or Ubiquitylation) refers to the post-translational modification of a protein by the covalent attachment (via an isopeptide bond) of one or more ubiquitin monomers. Ubiquitin (originally, Ubiquitous Immunopoietic Polypeptide) was first identified in 1975 as an 8.5 kDa protein of unknown function expressed universally in living cells. The basic functions of ubiquitin and the components of the ubiquitination pathway were elucidated in the early 1980s in groundbreaking work performed by Aaron Ciechanover, Avram Hershko and Irwin Rose for which the Nobel Prize in Chemistry was awarded in 2004.
Poly-ubiquitination, the process in which a chain of at least four ubiquitin peptides are attached to a lysine on a substrate protein, most commonly results in the degradation of the substrate protein via the proteasome. Apparently, at least four ubiquitins are required on a substrate protein in order for the proteasome to bind and therefore degrade the substrate (though there are examples of non-ubiquitinated proteins being targeted to the proteasome).
Mono-ubiquitination, the process in which a single ubiquitin peptide is bound to a substrate, initiates cell signaling by allowing other proteins that contain ubiquitin binding domains to interact with the mono-ubiquitinated substrate. Mono-ubiquitination has been associated with targeting of membrane proteins to the lysosome, for example.
The ubiquitylation system was initially characterised as an ATP-dependent proteolytic system present in cellular extracts. A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein substrate lysozyme in an ATP and Mg2+-dependent process. Multiple APF-1 molecules were linked to a single substrate molecule by an isopeptide linkage and conjugates were found to be rapidly degraded with the release of free APF-1. Soon after APF-1-protein conjugation was characterised, APF-1 was identified as ubiquitin. The carboxyl group of the C-terminal glycine residue of ubiquitin (Gly76) was identified as the moiety conjugated to substrate lysine residues.
