The proteasome is a large, multi-subunit protein complex responsible for the selective degradation of proteins in the cell. It plays a crucial role in maintaining cellular homeostasis by removing damaged, misfolded, or short-lived proteins. The process of protein turnover involves the recognition, unfolding, and degradation of target proteins by the proteasome.Recognition and selective degradation of specific proteins by the proteasome involve several steps:1. Ubiquitination: The first step in the recognition process is the covalent attachment of a small protein called ubiquitin to the target protein. This process is mediated by a series of enzymes, including ubiquitin-activating enzyme E1 , ubiquitin-conjugating enzyme E2 , and ubiquitin ligase E3 . The E3 ligase is responsible for substrate specificity, as it recognizes specific degradation signals, or "degrons," on the target protein. Multiple ubiquitin molecules are attached to the target protein, forming a polyubiquitin chain.2. Recognition by the proteasome: The 26S proteasome, the primary proteasome responsible for protein degradation, is composed of two main subcomplexes: the 20S core particle CP and the 19S regulatory particle RP . The 19S RP recognizes the polyubiquitinated target protein through its ubiquitin receptors. The polyubiquitin chain serves as a signal for the proteasome to selectively degrade the tagged protein.3. Deubiquitination and unfolding: Before degradation, the polyubiquitin chain is removed from the target protein by deubiquitinating enzymes DUBs associated with the 19S RP. The target protein is then unfolded by ATP-dependent unfoldases present in the 19S RP, which use the energy from ATP hydrolysis to unfold the protein and translocate it into the 20S CP.4. Degradation: The unfolded target protein is degraded within the 20S CP, which contains proteolytic active sites. These active sites cleave the protein into small peptides, which are then released from the proteasome and further degraded into amino acids by cellular peptidases.In summary, the proteasome recognizes and selectively degrades specific proteins in the process of protein turnover through a series of steps involving ubiquitination, recognition by the 19S regulatory particle, deubiquitination and unfolding, and degradation within the 20S core particle. This process ensures that damaged, misfolded, or short-lived proteins are efficiently removed from the cell, maintaining cellular homeostasis and proper functioning.