protein deneddylation

Definition

Target type: biologicalprocess

The removal of a ubiquitin-like protein of the NEDD8 type from a protein. [GOC:krc]

Protein deneddylation is a critical regulatory process that involves the removal of the ubiquitin-like protein NEDD8 from target proteins. NEDD8, short for Neural precursor cell expressed, developmentally downregulated 8, is a small protein that is covalently attached to lysine residues on target proteins, a process known as NEDDylation. This modification can alter the activity, stability, and localization of target proteins, playing a crucial role in various cellular processes, including cell cycle regulation, DNA replication, and signal transduction.

Deneddylation is carried out by a family of enzymes called deneddylases, also known as NEDP1/DEN1. These enzymes are cysteine proteases that specifically cleave the isopeptide bond between NEDD8 and its target protein. Deneddylases are highly conserved from yeast to humans, highlighting the importance of this process in cellular function.

The process of deneddylation typically involves the following steps:

1. **Recognition:** The deneddylase enzyme recognizes and binds to the NEDD8 moiety attached to the target protein.
2. **Catalytic cleavage:** The deneddylase utilizes its catalytic cysteine residue to cleave the isopeptide bond between NEDD8 and the target protein, releasing NEDD8.
3. **Release:** The deneddylase releases the free NEDD8 and the deneddylated target protein.

Deneddylation plays a crucial role in regulating various cellular processes by:

* **Reversing NEDDylation:** By removing NEDD8 from target proteins, deneddylation can reverse the effects of NEDDylation, restoring the protein to its original state.
* **Controlling protein activity:** Deneddylation can modulate the activity of target proteins by removing the NEDD8 modification, which can alter their function.
* **Regulating protein stability:** Deneddylation can affect the stability of target proteins by influencing their susceptibility to degradation.
* **Modulating protein localization:** Deneddylation can alter the subcellular localization of target proteins by influencing their interactions with other cellular components.

Dysregulation of deneddylation has been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. For instance, mutations in deneddylase genes have been associated with increased cancer cell proliferation and drug resistance. Therefore, understanding the molecular mechanisms of deneddylation and its regulation is crucial for developing new therapeutic strategies to target these diseases.'
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Proteins (1)

Compounds (1)