ubiquitin-dependent protein catabolic process via the C-end degron rule pathway

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the DesCEND (destruction via C-end degron) pathway. In the DesCEND pathway, C-terminal residues (C-end degrons) in substrates are recognized by Cul2-RING and Cul4-RING E3 ligases, whereupon the substrates are linked to ubiquitin and then delivered to the proteasome for degradation. C-end degrons can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. [PMID:29775578, PMID:29779948]

The C-end degron rule pathway is a crucial mechanism for ubiquitin-dependent protein catabolism, primarily targeting proteins with specific amino acid sequences at their C-termini. This pathway relies on the recognition of these degron motifs by specific E3 ligases, which are responsible for attaching ubiquitin chains to the target protein.

The process starts with the recognition of the degron sequence by an E3 ligase, often aided by adaptor proteins. These E3 ligases possess specific substrate binding domains that interact with the degron motif, ensuring the correct protein is targeted.

Once the degron is recognized, the E3 ligase facilitates the transfer of ubiquitin from a ubiquitin-conjugating enzyme (E2) to the target protein. This transfer involves a series of enzymatic steps, with the E3 ligase acting as a bridge between the E2 and the substrate protein.

The attachment of ubiquitin, a small protein, to the target protein serves as a signal for degradation. Ubiquitin itself can be linked to other ubiquitin molecules, forming polyubiquitin chains. These chains are recognized by the 26S proteasome, a large protein complex responsible for protein degradation.

The proteasome unfolds and degrades the ubiquitin-tagged protein into small peptides. These peptides can be recycled or further degraded. The C-end degron rule pathway is essential for regulating protein levels and ensuring proper cellular function. It is implicated in various cellular processes, including cell cycle control, signal transduction, and stress response. The specificity of the pathway arises from the unique degron sequences recognized by different E3 ligases, allowing for selective degradation of specific proteins.'
"

Proteins (1)

Compounds (1)