negative regulation of protein autoubiquitination

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of protein autoubiquitination. [GO_REF:0000058, GOC:bc, GOC:PARL, GOC:TermGenie, PMID:17237821]

Negative regulation of protein autoubiquitination is a critical cellular process that controls the stability and activity of proteins. It involves the removal or prevention of ubiquitin chains from a protein by deubiquitinating enzymes (DUBs) or by interfering with the ubiquitination machinery. Ubiquitination is a post-translational modification where a small protein called ubiquitin is attached to a target protein, often leading to its degradation by the proteasome. Autoubiquitination is a specific type of ubiquitination where a protein adds ubiquitin to itself.

Negative regulation of autoubiquitination is essential for maintaining protein homeostasis and proper cellular function. It prevents excessive degradation of proteins, allowing them to function correctly and for the appropriate duration. The process involves several mechanisms, including:

- **DUB activity:** DUBs are enzymes that specifically remove ubiquitin chains from proteins. They can cleave the ubiquitin chain directly, preventing degradation, or they can target specific ubiquitin linkages, influencing the signal for protein degradation.
- **Inhibition of E3 ligase activity:** E3 ubiquitin ligases are responsible for attaching ubiquitin to target proteins. Negative regulation can occur through direct inhibition of E3 ligases or by interfering with their binding to target proteins.
- **Competition with ubiquitin:** Some proteins can compete with ubiquitin for binding sites on target proteins, preventing ubiquitination.
- **Modification of target proteins:** Modifications like phosphorylation or acetylation can alter the target protein's structure or expose sites that prevent ubiquitination.

Dysregulation of negative regulation of protein autoubiquitination can lead to various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. For example, mutations in DUB genes have been linked to several cancers, while impaired autoubiquitination can contribute to the accumulation of misfolded proteins in neurodegenerative diseases.

Understanding the molecular mechanisms of negative regulation of protein autoubiquitination is crucial for developing therapeutic strategies targeting specific proteins involved in disease pathogenesis.'
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Proteins (1)

Compounds (3)