positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. [GOC:mah]

Positive regulation of proteasomal ubiquitin-dependent protein catabolic process is a fundamental cellular process that controls the degradation of proteins within the proteasome, a multi-protein complex responsible for protein turnover. This process is essential for maintaining cellular homeostasis, responding to cellular stress, and regulating various cellular functions.

The process begins with the tagging of target proteins with a polyubiquitin chain, a signal that marks them for degradation. Ubiquitination is a highly specific and tightly regulated process, involving a cascade of enzymes:

1. **Ubiquitin-activating enzymes (E1s):** These enzymes activate ubiquitin, a small protein, by attaching it to a high-energy thioester bond.
2. **Ubiquitin-conjugating enzymes (E2s):** These enzymes transfer activated ubiquitin from E1 to a target protein.
3. **Ubiquitin ligases (E3s):** These enzymes recognize specific target proteins and facilitate the transfer of ubiquitin from E2 to the target, forming a polyubiquitin chain.

The polyubiquitinated proteins then bind to the proteasome, a large, barrel-shaped complex composed of 26S subunits. The proteasome unfolds and degrades the ubiquitinated proteins into small peptides, which can be recycled or further degraded.

Positive regulation of this process enhances the efficiency and specificity of protein degradation. This can occur through various mechanisms, including:

- **Increased activity of E1, E2, or E3 enzymes:** This leads to a higher rate of ubiquitination and protein targeting to the proteasome.
- **Increased expression of proteasome subunits:** This allows for greater proteolytic capacity.
- **Removal of inhibitors of the proteasome:** This increases the accessibility of the proteasome to target proteins.
- **Activation of signaling pathways that promote ubiquitination:** This triggers the degradation of specific proteins involved in cellular processes, such as cell cycle regulation or stress response.

Dysregulation of positive regulation of proteasomal ubiquitin-dependent protein catabolic process can lead to various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. Therefore, understanding and manipulating this process is crucial for developing therapeutic strategies for these conditions.'
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Proteins (22)

Compounds (631)