FBX23 Activators

FBX23 activators, through their influence on protein synthesis and degradation pathways, indirectly enhance the functional activity of FBX23. Compounds such as Cycloheximide and Tunicamycin disrupt protein folding and glycosylation, respectively. This disruption leads to an increased pool of misfolded proteins, which could enhance the demand for FBX23-mediated ubiquitination as the cell seeks to maintain proteostasis. Similarly, proteasome inhibitors like MG132, Epoxomicin, Bortezomib, and Lactacystin increase the level of ubiquitinated proteins within the cell by preventing their degradation. This accumulation can signal a need to upregulate the ubiquitination process, enhancing the activity of ubiquitin ligases such as FBX23. In the case of MLN4924, by inhibiting NEDD8-activating enzyme, the drug can cause an increase in the substrates available for ubiquitination, which might indirectly stimulate the activity of F-box proteins including FBX23. PYR-41, although an inhibitor of ubiquitination, could also result in a feedback mechanism that enhances FBX23's role in a stressed cellular environment.

Thalidomide and its derivatives exert their effects by targeting certain proteins for degradation; the altered levels of these proteins can indirectly affect the ubiquitination cycle, heightening the role of FBX23 in this process. Furthermore, oxidative stress inducers like the oxidized form of glutathione and sodium arsenite can lead to protein misfolding, which may subsequently increase the requirement for FBX23-mediated ubiquitination.