What is Ubiquitin?

Ubiquitin is a small protein that is found in almost all cellular tissues in humans and other eukaryotic organisms, which helps to regulate the processes of other proteins in the body.

Through a process known as ubiquitination or ubiquitylation, an ubiquitin molecule can bind to a substrate protein, changing the way it functions. This can lead to a number of different outcomes.

It is most widely recognised for its role in apoptosis of proteins, earning it the title of the molecular “kiss of death” for proteins, although it also plays a major part in several other cellular processes related to the regulation of proteins.

History

It was first discovered in 1975 by a group of scientific researchers led by Goldstein. Shortly following this, substantial research was conducted to further characterize the protein and the related processes. The theory of ubiquitination was born during this time, sparking interest about the possibility of targeting specific cells to be degraded by the proteasome.

Aaron Ciechanover, Avram Hershko and Irwin Rose furthered this understanding in more recent research, which showed the possibility of cell cycle control to change certain biological processes, such as gene transcription and immune function. These breakthrough discoveries earned them the Nobel Prize in Chemistry in 2004.

Ubiquitination

Ubiquitination occurs when an ubiquitin molecule bonds to a substrate protein and is a type of post-translational modification.

This process involves three steps with specific groups of enzymes to perform them, which are:

• Activation with ubiquitin-activating enzymes (E1s)
• Conjugation with ubiquitin-conjugating enzymes (E2s)
• Ligation with ubiquitin ligases (E3s)

Through these steps, the ubiquitin molecule forms an isopeptide bond with the residue of lysine on the protein substrate respectively. This also occasionally happens by way of a peptide bond at the N-terminus.

This can occur with the attachment of a single ubiquitin protein, which is known as monoubiquitination, or several ubiquitin proteins forming a chain, known as polyubiquitination.

Function

The result of ubiquitination can vary significantly. As mentioned previously, the most common event is the degradation of the protein via the proteasome. However, it may also affect their activity, location or interactions with other proteins.

Ubiquitin can affect:

• Apoptosis (cell death)
• Cell division and multiplication
• Degeneration of neurons and muscular cells
• DNA transcription and repair
• Immune and inflammatory response
• Neural network morphogenesis
• Organelle biogenesis
• Processing of antigens
• Receptor modulation
• Ribosome biogenesis
• Stress response pathway
• Viral infection

Ubiquitin-Like Modifiers

There is an entirely family of proteins that interact with proteins in a similar way, which is referred to as ubiquitin-like modifiers.

The members of this family may differ significantly in the sequence, but possess a characteristic 3D structure with a folded shape and C-terminal glycine residue that defines the family.

Ubiquitin-like modifiers may produce similar results to ubiquitin although in some cases they can be distinctly different. For example, one member of this family called SUMO can bind to a protein “tagged” by ubiquitin for degradation, stabilizing it and preventing it from being sent to the proteasome.

References

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC432229/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1266097/
• http://www.sciencedirect.com/science/article/pii/S0167488904002356

Further Reading

• All Ubiquitin Content
• Ubiquitination (Ubiquitylation)
• Ubiquitin-Like Modifiers
• Ubiquitin and Diseases
• Ubiquitin Function and Variety

Written by

Yolanda Smith

Yolanda graduated with a Bachelor of Pharmacy at the University of South Australia and has experience working in both Australia and Italy. She is passionate about how medicine, diet and lifestyle affect our health and enjoys helping people understand this. In her spare time she loves to explore the world and learn about new cultures and languages.