regulation of protein monoubiquitination

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of protein monoubiquitination. [GOC:TermGenie, PMID:21931591]

Protein monoubiquitination is a highly regulated process that involves the covalent attachment of a single ubiquitin molecule to a target protein. This process plays a crucial role in various cellular functions, including protein degradation, signal transduction, DNA repair, and endocytosis.

The regulation of protein monoubiquitination is achieved through a complex interplay of several factors, including:

**1. E1 (Ubiquitin-Activating Enzyme):** E1 enzymes are responsible for activating ubiquitin by attaching it to a cysteine residue within its active site. This process requires ATP hydrolysis and results in the formation of a high-energy thioester bond between ubiquitin and E1.

**2. E2 (Ubiquitin-Conjugating Enzyme):** E2 enzymes transfer activated ubiquitin from E1 to their own active site, forming a thioester bond. E2 enzymes exhibit a diverse range of substrate specificities, contributing to the selectivity of monoubiquitination events.

**3. E3 (Ubiquitin Ligase):** E3 enzymes bind both ubiquitin-charged E2 enzymes and target proteins. They act as the primary determinants of substrate specificity and facilitate the transfer of ubiquitin from E2 to the target protein. E3 ligases employ a variety of mechanisms to recognize their substrates, including protein-protein interactions, post-translational modifications, and specific sequence motifs.

**4. Deubiquitinases (DUBs):** DUBs are a family of enzymes that remove ubiquitin from target proteins. They play a crucial role in regulating the stability of ubiquitin modifications and ensuring the reversibility of the process. DUBs exhibit a wide range of substrate specificities and can act in concert with E3 ligases to fine-tune the ubiquitin landscape.

**5. Ubiquitin Chain Topology:** The attachment of ubiquitin to a target protein can occur at different lysine residues on the ubiquitin molecule itself, resulting in the formation of ubiquitin chains with distinct topologies. These chains can have varying lengths and branching patterns, each influencing the cellular outcome of ubiquitination.

**6. Cellular Signaling Pathways:** Monoubiquitination is often integrated into signaling pathways, where it can act as a switch to modulate protein activity or stability. For example, monoubiquitination can promote the degradation of specific proteins, activate downstream signaling cascades, or alter protein trafficking.

**7. Post-Translational Modifications:** Monoubiquitination can be influenced by other post-translational modifications, such as phosphorylation or acetylation. These modifications can either enhance or inhibit ubiquitination, contributing to the fine-tuning of protein activity.

In conclusion, the regulation of protein monoubiquitination involves a multi-step process that is orchestrated by a diverse array of enzymes, ubiquitin chains, and cellular signaling pathways. This complex network ensures the precise control of protein function and stability, playing a critical role in maintaining cellular homeostasis and responding to various cellular stimuli.'
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Proteins (1)

Compounds (6)