proteasomal ubiquitin-independent protein catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds that is mediated by the proteasome but do not involve ubiquitin. [GOC:tb]

Proteasomal ubiquitin-independent protein catabolism is a complex process that involves the degradation of proteins by the proteasome, without the involvement of ubiquitin. This pathway is essential for maintaining cellular homeostasis, eliminating damaged or misfolded proteins, and regulating the abundance of specific proteins. Here is a detailed description of the process:

1. **Target Recognition:** Proteins targeted for degradation through this pathway often possess specific features that distinguish them from other proteins. These features can include:
* **N-terminal degradation signals:** Specific amino acid sequences at the N-terminus of the protein can signal its degradation.
* **Conformational changes:** Misfolded or damaged proteins often adopt altered conformations that expose specific degradation signals.
* **Specific protein domains:** Certain protein domains can be recognized by specific degradation machinery.

2. **Proteasome Binding:** Once recognized, the target protein interacts with the proteasome, a large multi-protein complex responsible for protein degradation. The proteasome is composed of a 20S core particle and two 19S regulatory particles. The 20S core particle contains proteolytic active sites responsible for protein breakdown, while the 19S regulatory particles recognize and bind to target proteins.

3. **Protein Unfolding and Translocation:** The 19S regulatory particle unfolds the target protein and translocates it into the 20S core particle. This process involves ATP hydrolysis and requires the assistance of chaperone proteins.

4. **Protein Degradation:** Inside the 20S core particle, the target protein is degraded into short peptides. The 20S core particle contains three distinct proteolytic activities:
* **Trypsin-like activity:** Cleaves peptide bonds after basic residues.
* **Chymotrypsin-like activity:** Cleaves peptide bonds after hydrophobic residues.
* **Peptidylglutamyl peptide hydrolase activity:** Cleaves peptide bonds after acidic residues.

5. **Peptide Release:** The resulting peptides are released from the proteasome and can be further degraded by other proteases or recycled for protein synthesis.

The ubiquitin-independent protein catabolic process plays a critical role in various cellular processes, including:
* **Cellular homeostasis:** Removal of damaged or misfolded proteins maintains cellular integrity and prevents the accumulation of toxic proteins.
* **Protein turnover:** Regulating the levels of specific proteins by degrading them when they are no longer needed.
* **Signal transduction pathways:** Degradation of proteins can influence signaling cascades and regulate cellular responses to stimuli.
* **Immune responses:** Degradation of pathogens and their products is essential for immune defenses.

This pathway is highly regulated and involves the interplay of various factors, including chaperones, proteasomal subunits, and regulatory proteins. Dysregulation of this pathway can contribute to a range of diseases, including cancer, neurodegenerative diseases, and inflammatory disorders.'
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Proteins (1)

Compounds (22)