Ubiquitin is a small regulatory protein found in the majority of eukaryotic tissues and is added to lysine residues of proteins as a post-translational modification.
The addition of ubiquitin can impact on protein regulation in a number of ways including degradation, cellular localization, protein interactions and activity. These modifications can have diverse effects on a number of major cellular processes such as apoptosis, cell cycle, immune regulation and DNA transcription and repair among many others.
- Ubiquitin is attached to lysine residues in the target protein by a series of 3 main reactions: Activation, performed by ubiquitin activating enzymes or E1’s
- Conjugation, performed by ubiquitin-conjugating enzymes or E2’s
- Ligation, performed by ubiquitin-ligases or E3’s
The manner in which ubiquitin is added determines the outcome for the protein. These modifications can include:
- Monubiquitination, the addition of a single ubiquitin to one lysine residue in the protein
- Multi-monoubiquitination, the addition of single ubiquitin molecules to multiple lysine residues in the target protein
- Polyubiquitination, the addition of multiple ubiquitin residues to a single lysine residue in the protein in the form of a chain which can take a number of different conformations.
These modifications alter cellular process in different ways. For example, monubiquitination can impact on membrane trafficking; however, some forms of polyubquitination can result in a protein being targeted for degradation via the proteasome. The ubiquitin pathway has been implicated in a number of genetic disorders and diseases including cancer and neurological diseases which result from the build-up of protein aggregates such as; Alzheimer’s disease, Parkinson’s disease and Huntingdon’s disease.
Examples of popular knockout cell lines for studying Ubiquitin-Conjugating Enzymes
UBE2A | UBE2E1 | UBE2H | UBE2Q1 |
UBE2B | UBE2E2 | UBE2J1 | UBE2W |
UBE2C | UBE2E3 | UBE2J2 | UBE2Z |
UBE2D1 | UBE2F | UBE2K | |
UBE2D2 | UBE2G1 | UBE2L6 | |
UBE2D4 | UBE2G2 | UBE2O |
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