Ubiquitin-activating enzymes, also known as E1 enzymes, play a crucial role in the ubiquitin-proteasome system, which regulates protein degradation in cells. These enzymes activate ubiquitin, a small protein that tags other proteins for degradation, by forming a high-energy thioester bond with it. This activation is the first step in a cascade that ultimately leads to the attachment of ubiquitin to target proteins. Once activated, ubiquitin-activating enzymes transfer ubiquitin to ubiquitin-conjugating enzymes (E2 enzymes), which then facilitate the transfer of ubiquitin to specific substrate proteins. This process is essential for maintaining cellular homeostasis, regulating various cellular functions, and responding to stress or damage.