CUL-7 Activators

The category of CUL7_HUMAN Activators refers to a group of compounds that can influence the activity of the CUL7 protein, which is a core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes. These complexes mediate the ubiquitination and subsequent proteasomal degradation of target proteins. It's important to note that these compounds do not directly "activate" CUL7, but rather interact with the broader ubiquitin-proteasome pathway, which can indirectly alter the function of CUL7. Most of the compounds listed in the table are proteasome inhibitors, including MG132, Bortezomib, Lactacystin, Epoxomicin, Carfilzomib, Marizomib, and Celastrol. These inhibitors prevent the degradation of ubiquitinated proteins by blocking the proteasome, the molecular machine that carries out this process. By halting the degradation of these proteins, these inhibitors can affect the activity of CUL7 and other proteins in the ubiquitin-proteasome pathway.

MLN4924 and Pyr-41 are unique in that they target earlier steps in the ubiquitination process. MLN4924 inhibits the NEDD8-activating enzyme (NAE), preventing the neddylation process, which is necessary for the activation of cullin proteins, including CUL7. Pyr-41, on the other hand, inhibits the ubiquitin-activating enzyme (E1), preventing the transfer of ubiquitin to E2 enzymes, a step that is crucial for the ubiquitination process. The remaining compounds, Thalidomide, IU1, and Nutlin-3, have more indirect effects on CUL7 activity. Thalidomide enhances the ubiquitination and degradation of certain proteins, which can indirectly influence CUL7. IU1 inhibits the proteasome-associated deubiquitinating enzyme USP14, potentially enhancing the degradation of proteins and indirectly influencing CUL7. Nutlin-3 affects CUL7 activity by inhibiting the interaction between p53 and MDM2, a protein that can be ubiquitinated by a complex involving CUL7.