positive regulation of protein K48-linked ubiquitination

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of protein K48-linked ubiquitination. [GOC:TermGenie, PMID:21931591]

Positive regulation of protein K48-linked ubiquitination is a complex process that plays a crucial role in regulating protein stability, signaling pathways, and cellular processes. It involves a cascade of events initiated by E1 ubiquitin-activating enzymes, which activate ubiquitin molecules by attaching them to a high-energy thioester bond. These activated ubiquitin molecules are then transferred to E2 ubiquitin-conjugating enzymes, which act as intermediates in the process. E3 ubiquitin ligases recognize specific target proteins and facilitate the transfer of ubiquitin from E2 enzymes to lysine residues on the target protein.

Ubiquitination can occur through different linkages, with K48-linked ubiquitination being a critical signal for protein degradation. In this process, multiple ubiquitin molecules are linked together via the lysine 48 (K48) residue on one ubiquitin to the lysine residue of the next ubiquitin, forming a polyubiquitin chain. This K48-linked polyubiquitin chain acts as a signal for the proteasome, a large protein complex responsible for degrading misfolded or damaged proteins.

Positive regulation of protein K48-linked ubiquitination involves factors that enhance the efficiency of this process. These factors can include:

* **Increased expression or activity of E1, E2, or E3 enzymes:** Higher levels of these enzymes can lead to increased ubiquitination rates.
* **Modification of E3 ligases:** Some post-translational modifications, such as phosphorylation or acetylation, can enhance the activity of E3 ligases, leading to increased ubiquitination.
* **Scaffolding proteins:** These proteins can bring E2 and E3 enzymes closer to their target proteins, facilitating ubiquitination.
* **Deubiquitinases:** While deubiquitinases typically remove ubiquitin chains, some deubiquitinases can specifically enhance K48-linked ubiquitination by removing competing ubiquitin chains or promoting the formation of polyubiquitin chains.

The positive regulation of protein K48-linked ubiquitination is a tightly regulated process, ensuring that proteins destined for degradation are appropriately targeted. Dysregulation of this process can lead to various diseases, including cancer and neurodegenerative disorders. Understanding the intricate details of this pathway is crucial for developing therapeutic strategies to modulate protein degradation and address these diseases.'
"

Proteins (1)

Compounds (8)