protein K48-linked ubiquitination

Definition

Target type: biologicalprocess

A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation. [GOC:cvs, PMID:15556404]

K48-linked ubiquitination is a critical process in cellular regulation, playing a key role in protein degradation, signal transduction, and DNA repair. It involves the covalent attachment of a small protein, ubiquitin, to a target protein through a specific lysine residue.

The process begins with the activation of ubiquitin by the E1 enzyme, which utilizes ATP to form a high-energy thioester bond between ubiquitin and the active site cysteine of E1. This activated ubiquitin is then transferred to the active site cysteine of an E2 ubiquitin-conjugating enzyme, forming a transient E2-ubiquitin thioester intermediate.

The E2 enzyme interacts with an E3 ubiquitin ligase, which recognizes the target protein and facilitates the transfer of ubiquitin from E2 to the target protein. This transfer involves a specific lysine residue on the target protein, usually within a lysine-containing motif called a degron.

K48-linked polyubiquitination occurs when multiple ubiquitin molecules are attached to the target protein in a linear chain, with the C-terminus of each ubiquitin linked to the lysine residue at position 48 (K48) of the subsequent ubiquitin molecule. This K48-linked polyubiquitin chain acts as a signal for the proteasome, a large protein complex responsible for degrading misfolded or damaged proteins.

The proteasome recognizes and binds to the K48-linked polyubiquitin chain, and then unfolds and degrades the target protein into small peptides. This process ensures that misfolded or damaged proteins are removed from the cell, preventing their accumulation and potential harmful effects.

In addition to protein degradation, K48-linked ubiquitination is involved in various cellular processes. For example, it regulates signal transduction pathways by modulating the activity of signaling proteins. It also plays a role in DNA repair by targeting damaged DNA segments for removal and repair.

Overall, K48-linked ubiquitination is a highly regulated and essential process in cellular homeostasis, playing a vital role in protein degradation, signal transduction, and DNA repair.'
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Proteins (1)

Compounds (2)