protein linear polyubiquitination

Definition

Target type: biologicalprocess

A protein ubiquitination process in which a linear polymer of ubiquitin, formed by the amino-terminal methionine (M1) of one ubiquitin molecule and by the carboxy-terminal glycine (G76) of the next, is added to a protein. [GOC:jsg, GOC:sp, PMID:21455173, PMID:21455180, PMID:21455181]

Protein linear polyubiquitination is a complex process that involves the covalent attachment of ubiquitin (Ub) monomers to lysine residues within target proteins. This process plays a critical role in various cellular processes, including protein degradation, signal transduction, and DNA repair. Linear polyubiquitination is characterized by the formation of ubiquitin chains where each ubiquitin molecule is linked to the next through the C-terminal glycine residue of one ubiquitin to the lysine residue at position 63 (K63) of the following ubiquitin. This linkage creates a linear chain with a distinct structure and function compared to other polyubiquitin chain types, such as K48-linked chains.

The process of linear polyubiquitination involves a series of enzymatic steps:

1. **Ubiquitin activation:** The first step involves the activation of ubiquitin by an E1 ubiquitin-activating enzyme. This enzyme uses ATP to form a high-energy thioester bond between ubiquitin and a cysteine residue on the E1 enzyme.

2. **Ubiquitin conjugation:** The activated ubiquitin is then transferred to an E2 ubiquitin-conjugating enzyme, also via a thioester bond. E2 enzymes are responsible for mediating the transfer of ubiquitin to target proteins.

3. **Ubiquitin ligation:** Finally, a specific E3 ubiquitin ligase recognizes both the target protein and the E2~ubiquitin complex, facilitating the transfer of ubiquitin to the target protein. E3 ligases are responsible for determining the type of ubiquitin chain formed and the specific lysine residue on the target protein that is modified.

Linear polyubiquitination mediated by specific E3 ligases, such as the linear ubiquitin chain assembly complex (LUBAC), plays a crucial role in various cellular functions:

- **NF-κB signaling:** Linear polyubiquitination of the NF-κB essential modulator (NEMO) activates the NF-κB signaling pathway, which is involved in regulating immune responses, inflammation, and cell survival.

- **DNA damage response:** Linear polyubiquitination is involved in the DNA damage response by modulating the activity of DNA repair proteins.

- **Antiviral immunity:** Linear polyubiquitination is critical for antiviral immunity by facilitating the degradation of viral proteins and the activation of interferon signaling pathways.

- **Autophagy:** Linear polyubiquitination plays a role in regulating autophagy, a process that involves the degradation of cellular components.

Overall, linear polyubiquitination is a highly regulated and specific process that plays a critical role in various cellular processes. Its distinct structure and function differentiate it from other types of polyubiquitination, highlighting its importance in maintaining cellular homeostasis and regulating diverse cellular functions.'
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Proteins (3)

Compounds (1)