Ubiquitination

Degradation of proteins by ubiquitin (also called ubiquitous immunopoietic polypeptide) and proteasomes. Ubiquitination (ubiquitylation) is a versatile post-translational modification to control protein levels in cells and modulate cellular state to allow adaptation under stress. In fact, this secondary modification is crucial for the cellular response to DNA-damaging agents, including ionizing radiation (IR).

Three enzyme families are involved in ubiquitination:

E1 (ubiquitin-activating protein).

E2 (ubiquitin-conjugating enzyme)

E3 (ubiquitin-protein ligase).

Only one E1 enzyme exists. About 30 variants of the E2 family are known, and more than 100 enzymes of the E3 family.

First, ubiquitin is activated by E1. Then, the activated polypeptide is again converted into a thioester bond with E2. Finally, ubiquitin is bound to the target protein by E3.

In principle, all proteins can be degraded by ubiquitin and proteasomes, but especially proteins involved in inflammatory processes or proteins that regulate the cell cycle.

The protein characterized by ubiquitin is transferred to the barrel-shaped complex of the proteasome, where the actual degradation of proteins into smaller peptides occurs.

Example: NF-kB is a transcription factor for genes whose products are involved in inflammatory responses. The inhbitor of NF-kB can be degraded by ubiquitin; thus NF-kB is released. This can lead to the transcription of target genes encoding inflammatory mediators.

1. Yi J et al (2007) Emerging roles for ubiquitin and protein degradation in neuronal function. Pharmacol Rev 59: 14-39