protein K63-linked deubiquitination

Definition

Target type: biologicalprocess

A protein deubiquitination process in which a K63-linked ubiquitin chain, i.e. a polymer of ubiquitin formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is removed from a protein. [GOC:mah, PMID:19202061, PMID:19214193]

Protein K63-linked deubiquitination is a crucial regulatory mechanism in cellular processes, particularly in signal transduction, DNA repair, and inflammation. K63-linked polyubiquitination involves the attachment of ubiquitin molecules to a target protein via their lysine 63 residue, forming a chain that does not typically lead to proteasomal degradation. Instead, these chains act as signaling platforms, recruiting specific effector proteins and modulating the activity of the target protein. Deubiquitinases (DUBs) play a critical role in counteracting this process by removing K63-linked ubiquitin chains.

The process of K63-linked deubiquitination can be summarized in the following steps:

1. **Recognition and Binding:** DUBs possess specific domains that recognize and bind to K63-linked ubiquitin chains. These domains often exhibit high affinity for the unique structural features of K63 linkages.
2. **Cleavage of the Isopeptide Bond:** Once bound, the DUB catalytic domain cleaves the isopeptide bond between the ubiquitin molecule and the target protein or between adjacent ubiquitin molecules within the chain. This process is typically highly specific and involves the hydrolysis of the isopeptide bond.
3. **Release of Free Ubiquitin and Target Protein:** The cleavage event releases free ubiquitin molecules and the target protein, which can now function without the attached ubiquitin chains.

The functional consequences of K63-linked deubiquitination vary depending on the target protein and the cellular context. For instance, in signaling pathways, DUBs can remove K63-linked ubiquitin chains from receptor proteins, thereby terminating the signal transduction cascade. In DNA repair, DUBs are involved in the removal of K63-linked ubiquitin from DNA repair proteins, facilitating the repair process. In inflammation, DUBs can modulate the activity of inflammatory signaling molecules by removing K63-linked ubiquitin chains.

The regulation of K63-linked deubiquitination is tightly controlled, and dysregulation can lead to various diseases, including cancer, neurodegeneration, and immune disorders. The complex interplay between ubiquitination and deubiquitination is a key determinant of cellular homeostasis and the intricate balance of signaling pathways.'
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Proteins (6)

Compounds (19)