positive regulation of protein ubiquitination

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the addition of ubiquitin groups to a protein. [GOC:mah]

Positive regulation of protein ubiquitination is a complex cellular process that involves a cascade of enzymatic reactions leading to the attachment of ubiquitin, a small protein, to target proteins. Ubiquitination plays a crucial role in various cellular processes, including protein degradation, signal transduction, DNA repair, and immune response.

The process of positive regulation of protein ubiquitination is initiated by the activation of an E1 ubiquitin-activating enzyme. E1 binds to ubiquitin and uses ATP to activate it, forming a high-energy thioester bond. The activated ubiquitin is then transferred to an E2 ubiquitin-conjugating enzyme. E2s are responsible for recognizing and binding to specific target proteins. The final step involves the transfer of ubiquitin from the E2 to the target protein, catalyzed by an E3 ubiquitin ligase. E3s act as the specificity determinants of the ubiquitination process, recognizing specific protein substrates and facilitating the formation of an isopeptide bond between ubiquitin and a lysine residue on the target protein.

The ubiquitination process can be regulated at multiple levels. One mechanism involves the regulation of the expression and activity of E1, E2, and E3 enzymes. Another level of regulation involves the interaction between ubiquitin ligases and specific protein substrates. These interactions can be modulated by various factors, including phosphorylation, acetylation, and other post-translational modifications.

The attachment of ubiquitin to target proteins can lead to a variety of cellular outcomes. Mono-ubiquitination, the addition of a single ubiquitin molecule, can affect protein trafficking, localization, and DNA repair. Poly-ubiquitination, the addition of multiple ubiquitin molecules, can lead to protein degradation via the proteasome pathway. The type of poly-ubiquitin chain formed, either K48-linked or K63-linked, determines the fate of the target protein. K48-linked chains target proteins for degradation, while K63-linked chains play roles in signal transduction and DNA repair.

Positive regulation of protein ubiquitination ensures the efficient and precise execution of these diverse cellular functions. It plays a crucial role in maintaining cellular homeostasis, responding to environmental stimuli, and regulating various signaling pathways. Dysregulation of protein ubiquitination can lead to a variety of diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.'
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Proteins (18)

Compounds (557)