Ubiquitylation, also referred to as ubiquitination*, is the process of attaching ubiquitin, a small protein found in almost all tissues of eukaryotic organisms, to another targeted protein. Ubiquitylation can change the activity of a protein or change that protein’s role within the cell, although the most common association scientists make with this process is that it marks targeted proteins for degradation. The theory is that ubiquitylation helps cells to track the use of a molecule so that the molecule is more likely to be digested when it has been around for a long time.
Ubiquitin attaches to lysine groups of target proteins through the activity of a ubiquitin ligase (E3) and a ubiquitin-conjugating enzyme (E2). These proteins facilitate the activation and transfer of ubiquitin either directly to the target protein or to other ubiquitin proteins that already have been attached to the target protein. Some proteins are ubiquitylated only once, creating an additional functional group at the lysine site. Such a single instance of ubiquitylation on a protein doesn’t necessarily mark it for degradation through the proteasome pathway. Rather, the target protein’s function can be altered by a single ubiquitin because of a change in functional group or protein binding site.
When a chain of more than one ubiquitin molecule attaches to the same target protein, that protein is said to be poly-ubiquitylated. Poly-ubiquitin chains appear to serve multiple purposes, of which the best understood is marking target proteins for degradation through the proteasome. There are seven ways in which one ubiquitin protein can bind to another, meaning that the poly-ubiquitin chains can take on a wide diversity of shapes, each of which may signal a different outcome.
Ubiquitin is found in almost all tissues of eukaryotic organisms and can be found tagged to almost any protein. It is evolutionarily advantageous for all cells of eukaryotic organisms to use the process of ubiquitylation because it removes breaking, worn or sub-functional proteins from cells before the proteins cease functioning entirely. A system that pre-emptively removes proteins from use and tags them for protein recycling keeps cells healthy.
The process of ubiquitylation is still not fully understood, and is therefore understandably an area of intense academic and commercial interest. Avacta Life Sciences will soon launch a catalogue of products including a toolbox of ubiquitylation Affimer reagents, providing a set of revolutionary new detection tools for life scientists to research ubiquitylation (or indeed ubiquitination). Further information on the launch of this exciting product range will be published soon!
* The debate between whether to use ‘ubiquitylation’ (chosen by analogy with the process of adding methane as a methyl group in methylation) or ‘ubiquitination’ (self-explanatory, although perhaps less chemically accurate) raises passions around the world. We don’t aim to settle this debate – just to give you the tools to study the biology.