I am wondering why some protein inhibitors increase the levels of target protein and still known as their inhibitors? For example MCL1 inhibitor S63845 increase the levels of MCL1 in tumor cells (Kotschy et al., Nature 538, 477–482). I understands that these inhibitors mostly act to inhibit protein-protein interactions. Like, in this case S63845 inhibits interaction of MCL1 with BAK and BAX, thereby facilitates the availability of BAK and BAX for downstream apoptotic pathway. But, It always confuses me why it is known as a inhibitor of MCL1?
The amount of the protein present in the cell does not equate with the amount of that protein's activity if there is an inhibitor present. The cell may respond to the lack of the target protein's activity in the presence of the inhibitor by upregulating the synthesis of that protein. Thus, more of it is made, but without effect because of the inhibitor.
The amount of the protein present in the cell does not equate with the amount of that protein's activity if there is an inhibitor present. The cell may respond to the lack of the target protein's activity in the presence of the inhibitor by upregulating the synthesis of that protein. Thus, more of it is made, but without effect because of the inhibitor.
Hi there,
As Adam already mentioned, upregulation of the protein level is a way for the cell to compensate the inhibition of the protein activity.
Thank you Drs. Shapiro and Linger for your answers.
Since an inhibitor can inhibits the activity of a particular protein either through its downregulation or upregulation, I have a further question that what are the factors which influence whether an inhibitor will act through downregulation or upregulation of a protein? Is it possible that a inhibitor doesn't influence protein levels and still it inhibits its activity? I will appreciate if you could provide me some related references.
Thank you in advance for your invaluable answers
It depends on the level at which he inhibitor is inhibiting, transcription, translation or post translation, . Even a co-factor binding is imparted the protein can not function.I am interested in the studies, how we can intervene at the level of protein -protein interactions thereby inhibiting a specific pathway . In such instances Protein concentration WB or ELISA will not indicate the functional impairment.End point assay can help in the understanding the degree of inhibition. That is the reason why we say proteins are functional molecule,
- Badges
- Science topic
- Similar topics
- Biological Science
- Molecular Biology
- Biomolecules
- Proteins