deNEDDylase activity

Definition

Target type: molecularfunction

An isopeptidase activity that cleaves NEDD8 from a target protein to which it is conjugated. [GOC:mah, PMID:25628956]

DeNEDDylase activity refers to the enzymatic removal of the ubiquitin-like protein NEDD8 (Neural precursor cell expressed developmentally downregulated 8) from target proteins. This process, also known as deneddylation, plays a crucial role in regulating the activity of a diverse range of cellular processes. NEDD8 is conjugated to lysine residues on target proteins, a process termed NEDDylation. This modification can alter the activity, stability, or localization of the target protein. DeNEDDylation counteracts NEDDylation, effectively reversing the effects of NEDD8 conjugation.

DeNEDDylation is carried out by a family of enzymes known as NEDD8-specific proteases (DEN1, SENP1-SENP8, and COP9 signalosome). These enzymes recognize and bind to the NEDD8 moiety attached to the target protein. Through a complex enzymatic mechanism, they cleave the isopeptide bond between NEDD8 and the target protein, releasing NEDD8 and restoring the target protein to its unmodified state.

DeNEDDylation is essential for maintaining cellular homeostasis. It serves several key functions:
* **Regulation of protein activity:** DeNEDDylation can modulate the activity of target proteins by removing NEDD8, which can either activate or inhibit the protein's function. For example, deNEDDylation of the cullin-RING ligase (CRL) family of E3 ubiquitin ligases can activate their ubiquitin ligase activity, leading to the degradation of target proteins.
* **Control of protein stability:** NEDDylation can influence protein stability by regulating their susceptibility to proteasomal degradation. DeNEDDylation can prevent premature protein degradation, ensuring that proteins remain functional for the required duration.
* **Regulation of protein localization:** NEDDylation can affect protein localization by altering their interactions with cellular components. DeNEDDylation can reverse these changes, ensuring that proteins are directed to their correct cellular compartments.

In summary, deNEDDylase activity is a critical regulatory process that plays a vital role in cellular function. It controls the activity, stability, and localization of target proteins by removing NEDD8 from these proteins. This process is essential for maintaining cellular homeostasis and orchestrating a wide range of cellular processes.'
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Proteins (4)

Compounds (8)