How are proteins tagged for degradation?

Proteins are tagged for degradation primarily through the process of ubiquitination. This involves the covalent attachment of a small protein called ubiquitin to the target protein. This tagging mechanism serves as a signal for the cellular destruction system, specifically the proteasome, which recognizes the proteins marked with ubiquitin and facilitates their breakdown.

The ubiquitination process typically involves a cascade of enzymes – E1 activating enzymes, E2 conjugating enzymes, and E3 ligases, which ultimately link ubiquitin to the substrate protein. A polyubiquitin chain, particularly one involving multiple ubiquitin molecules, is often necessary for the recognition and subsequent degradation of the protein by the proteasome.

Understanding ubiquitination is critical because it plays a crucial role in regulating various cellular processes, including the cell cycle, DNA repair, and responses to oxidative stress, by controlling protein levels and functionality.