protein ubiquitination

Definition

Target type: biologicalprocess

The process in which one or more ubiquitin groups are added to a protein. [GOC:ai]

Protein ubiquitination is a fundamental cellular process involving the covalent attachment of ubiquitin, a small, highly conserved protein, to target proteins. This process plays a crucial role in regulating a vast array of cellular functions, including protein degradation, signal transduction, DNA repair, and immune responses.

Ubiquitination occurs through a three-step enzymatic cascade:

1. Activation: The ubiquitin molecule is activated by the E1 enzyme, an ubiquitin-activating enzyme. This involves the formation of a high-energy thioester bond between the carboxyl terminus of ubiquitin and a cysteine residue on the E1 enzyme.

2. Conjugation: The activated ubiquitin is transferred from the E1 enzyme to an E2 enzyme, an ubiquitin-conjugating enzyme. This transfer is also mediated by a thioester bond, with the ubiquitin now attached to a cysteine residue on the E2 enzyme.

3. Ligation: The E2 enzyme interacts with an E3 enzyme, an ubiquitin ligase, which recognizes and binds to the target protein. The E3 enzyme facilitates the transfer of ubiquitin from the E2 enzyme to a specific lysine residue on the target protein. This process forms an isopeptide bond between the carboxyl terminus of ubiquitin and the epsilon amino group of the target protein lysine.

The ubiquitination process can occur as a single ubiquitin molecule attached to the target protein (monoubiquitination), or it can involve the attachment of multiple ubiquitin molecules (polyubiquitination). Polyubiquitination can be linear, where ubiquitin molecules are linked in a single chain, or branched, where ubiquitin molecules are attached to each other in a more complex manner.

The type of ubiquitin chain formed determines the fate of the target protein. For example, polyubiquitination with Lys48-linked chains typically targets the protein for degradation by the proteasome, a protein complex responsible for breaking down misfolded or damaged proteins. Other ubiquitin chain types, such as Lys63-linked chains, are involved in signaling pathways and DNA repair.

Ubiquitination is a highly regulated and dynamic process, with various factors influencing the selection of target proteins, the type of ubiquitin chain formed, and the downstream cellular responses. Dysregulation of ubiquitination can lead to various diseases, including cancer, neurodegenerative disorders, and immune deficiencies. Therefore, understanding the intricacies of this process is crucial for developing therapeutic strategies for these diseases.'
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Proteins (40)

Compounds (1,443)