ubiquitin-dependent protein catabolic process via the multivesicular body sorting 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 multivesicular body (MVB) sorting pathway; ubiquitin-tagged proteins are sorted into MVBs, and delivered to a lysosome/vacuole for degradation. [GOC:jl, PMID:11511343]

Ubiquitin-dependent protein catabolic process via the multivesicular body (MVB) sorting pathway is a critical cellular process responsible for the selective degradation of proteins within lysosomes. This pathway is particularly important for removing misfolded, damaged, or short-lived proteins, ensuring proper cellular function and homeostasis.

Here's a detailed breakdown of the process:

1. **Protein Ubiquitylation:** The first step involves the tagging of target proteins with ubiquitin, a small protein that serves as a signal for degradation. This process is carried out by a cascade of enzymes: E1, E2, and E3 ligases. E1 activates ubiquitin, E2 carries it to the target protein, and E3 ligases specifically recognize and attach ubiquitin to the protein substrate. The addition of multiple ubiquitin molecules (polyubiquitylation) creates a signal that marks the protein for degradation.

2. **Sorting into Endosomes:** Ubiquitylated proteins are then sorted into early endosomes, membrane-bound compartments within the cell. These endosomes are dynamic and undergo maturation, transitioning into late endosomes.

3. **MVB Formation:** During late endosome maturation, intraluminal vesicles (ILVs) bud from the limiting membrane of the late endosome. These ILVs are small, membrane-enclosed vesicles that encapsulate the ubiquitinated proteins destined for degradation. The formation of ILVs is driven by the ESCRT (Endosomal Sorting Complexes Required for Transport) machinery, a series of protein complexes that act in a sequential manner to recognize and package ubiquitinated proteins into the ILVs.

4. **Fusion with Lysosomes:** The late endosome, now packed with ILVs containing the ubiquitinated proteins, matures further and fuses with lysosomes. Lysosomes are acidic organelles containing hydrolytic enzymes that break down macromolecules.

5. **Protein Degradation:** The fusion of the late endosome with the lysosome delivers the ILVs and their cargo to the lysosomal lumen. The acidic environment and hydrolytic enzymes within the lysosome degrade the ubiquitinated proteins into their constituent amino acids, completing the catabolic process.

This pathway plays a crucial role in various cellular functions, including:

* **Quality Control:** It removes misfolded or damaged proteins that can disrupt cellular processes.
* **Regulation of Cellular Signaling:** It regulates the lifespan of signaling proteins, controlling the duration and strength of signaling pathways.
* **Immune Response:** It is involved in antigen processing and presentation, enabling the immune system to recognize and respond to pathogens.
* **Developmental Processes:** It contributes to developmental events by regulating protein turnover during cell differentiation and morphogenesis.

Dysregulation of this pathway can lead to various diseases, including neurodegenerative disorders, cancer, and immune system dysfunction.'
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Proteins (2)

Compounds (116)