negative regulation of protein K63-linked ubiquitination

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of protein K63-linked ubiquitination. [GOC:TermGenie]

Negative regulation of protein K63-linked ubiquitination is a crucial process that controls the stability, localization, and activity of various proteins by modulating their K63-linked polyubiquitination status. K63-linked ubiquitination, a non-proteolytic form of ubiquitination, is a dynamic process involving the attachment of ubiquitin chains linked through lysine 63 of ubiquitin. These chains often act as signaling platforms, recruiting downstream proteins and modulating protein interactions.

The negative regulation of this process is essential for maintaining cellular homeostasis and preventing aberrant signaling. It involves a complex interplay of enzymes, including deubiquitinases (DUBs) and ubiquitin ligases (E3 ligases), which act in concert to remove or prevent the formation of K63-linked ubiquitin chains.

**Deubiquitinases (DUBs)** play a critical role in removing K63-linked ubiquitin chains from target proteins. DUBs are a diverse group of enzymes with distinct substrate specificities and catalytic mechanisms. They hydrolyze the isopeptide bond between ubiquitin and its target protein, leading to the removal of ubiquitin chains and the restoration of the protein's original state.

**Ubiquitin ligases (E3 ligases)** can also contribute to the negative regulation of K63-linked ubiquitination by promoting the formation of ubiquitin chains that are incompatible with K63-linked ubiquitination or by targeting K63-linked ubiquitin chains for degradation. This process involves the recruitment of specific E3 ligases that are capable of recognizing and binding to K63-linked ubiquitin chains. These E3 ligases can then promote the attachment of other types of ubiquitin chains, such as K48-linked chains, which typically target proteins for proteasomal degradation.

**Factors influencing negative regulation of protein K63-linked ubiquitination:**

- **Cellular context:** The negative regulation of K63-linked ubiquitination can vary depending on the cellular context, such as the type of cell, its developmental stage, and the presence of external stimuli.
- **Specific protein targets:** Different proteins have distinct requirements for K63-linked ubiquitination, and the mechanisms regulating their ubiquitination status can vary accordingly.
- **Signaling pathways:** K63-linked ubiquitination is involved in various signaling pathways, and its regulation is tightly linked to the activation and inactivation of these pathways.

In summary, negative regulation of protein K63-linked ubiquitination is a complex process involving a delicate balance of DUBs and E3 ligases, ensuring the proper control of protein stability, localization, and activity. This intricate regulation plays a crucial role in maintaining cellular homeostasis and preventing aberrant signaling, ultimately contributing to overall cell function and survival.'
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Proteins (2)

Compounds (20)