proteasome-mediated ubiquitin-dependent 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, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. [GOC:go_curators]

The proteasome-mediated ubiquitin-dependent protein catabolic process is a highly regulated and essential cellular pathway responsible for the degradation of proteins that are damaged, misfolded, or no longer needed. This process plays a crucial role in maintaining cellular homeostasis and ensuring proper cellular function. Here's a detailed description:

**1. Ubiquitination: Tagging Proteins for Degradation**

* Proteins targeted for degradation are first tagged with a small protein called ubiquitin. This process, known as ubiquitination, involves a series of enzymatic reactions.
* **E1 (Ubiquitin Activating Enzyme):** E1 activates ubiquitin by attaching it to itself using ATP.
* **E2 (Ubiquitin Conjugating Enzyme):** E2 receives ubiquitin from E1 and transfers it to a target protein.
* **E3 (Ubiquitin Ligase):** E3 recognizes specific target proteins based on their degradation signals (e.g., misfolding, damaged regions) and brings them into close proximity with E2 to facilitate the attachment of ubiquitin.
* Multiple ubiquitin molecules are linked together to form a polyubiquitin chain, which acts as a signal for proteasomal degradation.

**2. Proteasome Recognition and Degradation**

* The proteasome, a large, barrel-shaped protein complex, is the cellular machinery responsible for protein degradation.
* The proteasome recognizes and binds to proteins tagged with polyubiquitin chains.
* The proteasome unfolds the target protein, threading it through a central channel lined with proteolytic enzymes.
* These enzymes cleave the unfolded protein into short peptides, typically 7-8 amino acids long.

**3. Ubiquitin Recycling**

* The ubiquitin molecules are removed from the degraded protein and recycled for future rounds of ubiquitination.

**Key Features of the Proteasome-Mediated Protein Degradation Pathway:**

* **Specificity:** E3 ubiquitin ligases provide specificity by recognizing unique degradation signals on target proteins, ensuring the degradation of only those proteins destined for destruction.
* **Regulation:** Ubiquitination and proteasome activity are tightly regulated to prevent the degradation of essential proteins.
* **Dynamic:** The ubiquitin-proteasome system is highly dynamic and can respond quickly to changes in cellular conditions, such as stress, nutrient availability, or growth signals.

**Biological Significance:**

* **Cell Cycle Control:** The proteasome degrades proteins that regulate cell cycle progression, ensuring proper timing and coordination of cell division.
* **Signal Transduction:** The proteasome degrades signaling proteins, thereby controlling the duration and intensity of cellular responses to various stimuli.
* **DNA Repair:** The proteasome removes damaged or misfolded proteins involved in DNA repair, ensuring the integrity of the genome.
* **Immune Response:** The proteasome plays a crucial role in the generation of antigens for the immune system.
* **Protein Quality Control:** The proteasome degrades misfolded proteins, preventing the accumulation of toxic aggregates.

**Clinical Relevance:**

* **Disease:** Dysregulation of the ubiquitin-proteasome system has been implicated in several diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.
* **Drug Development:** Targeting the ubiquitin-proteasome system is a promising strategy for developing new therapies for various diseases.'
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Proteins (63)

Compounds (674)