protein autoubiquitination

Definition

Target type: biologicalprocess

The ubiquitination by a protein of one or more of its own amino acid residues, or residues on an identical protein. Ubiquitination occurs on the lysine residue by formation of an isopeptide crosslink. [GOC:ai]

Protein autoubiquitination is a fundamental cellular process where a protein directly adds ubiquitin molecules to itself. Ubiquitin is a small, highly conserved protein that acts as a molecular tag, directing proteins to various cellular destinations and influencing their fate. This process plays a crucial role in regulating a diverse range of cellular processes, including:

* **Protein Degradation:** Ubiquitination can target proteins for degradation by the proteasome, a cellular machinery that breaks down unwanted or damaged proteins.
* **Signal Transduction:** Autoubiquitination can alter protein activity and stability, impacting downstream signaling pathways.
* **DNA Repair:** Autoubiquitination is involved in the recruitment and activation of DNA repair enzymes, ensuring genomic integrity.
* **Cell Cycle Control:** This process regulates the progression of the cell cycle, ensuring proper DNA replication and cell division.

**Mechanism of Autoubiquitination:**

The process of autoubiquitination involves a series of steps:

1. **Activation:** The ubiquitin molecule is activated by an E1 ubiquitin-activating enzyme, forming a high-energy thioester bond.
2. **Conjugation:** The activated ubiquitin is transferred to an E2 ubiquitin-conjugating enzyme, which acts as an intermediary.
3. **Ligation:** The E2 enzyme interacts with an E3 ubiquitin ligase, which specifically recognizes and binds to the target protein. The E3 ligase facilitates the transfer of ubiquitin from the E2 to the target protein.

**Types of Autoubiquitination:**

There are various types of ubiquitination, including:

* **Mono-ubiquitination:** A single ubiquitin molecule is attached to the target protein.
* **Poly-ubiquitination:** Multiple ubiquitin molecules are linked together, forming a ubiquitin chain.
* **Multi-mono-ubiquitination:** Several ubiquitin molecules are attached to different lysine residues on the target protein.

The specific type of ubiquitin chain and its linkage determine the fate of the target protein.

**Regulation of Autoubiquitination:**

Autoubiquitination is tightly regulated to ensure proper cellular function. This regulation involves:

* **Substrate Specificity:** E3 ligases have distinct substrate preferences, ensuring that specific proteins are targeted for ubiquitination.
* **Post-translational Modifications:** Various modifications, such as phosphorylation, acetylation, and methylation, can influence autoubiquitination.
* **Ubiquitin Binding Proteins:** Proteins that bind to ubiquitin can modulate the activity of ubiquitin ligases or target proteins.

**Dysregulation of Autoubiquitination:**

Aberrant autoubiquitination is linked to various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.

**Conclusion:**

Protein autoubiquitination is a highly complex and essential cellular process that regulates a broad range of cellular functions. Understanding the intricate mechanisms of autoubiquitination is crucial for deciphering the underlying causes of various diseases and developing targeted therapeutic strategies.'
"

Proteins (3)

Compounds (22)