When a Drug Mimics a Natural Signal, What Else Happens?

In the world of cell communication, it’s not always what a signal is, but how it’s delivered. Our research, published in the journal Oncogene, explores this concept by comparing how cells respond to a natural signal versus a man-made one.

The paper, "Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling," focuses on a family of proteins called cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2). These proteins are known to play a central role in how cells communicate, particularly in immune and inflammatory responses. We know that a natural signal, such as a CD30 receptor being activated on the surface of a cell, can cause these proteins to be degraded. Scientists have also developed synthetic compounds, called Smac mimetics, that can do the same thing.

Our study asked a key question: does the synthetic compound truly mimic the natural signal? Using a specialized technique to analyze newly transcribed RNA, we compared the genetic responses triggered by both stimuli.

We found that while both the natural and synthetic signals degraded the c-IAP proteins and activated the same cell signaling pathways, the overall cellular response was not identical. Our research uncovered a new and unexpected role for these proteins: they also have a hand in regulating the ribosome, the cell’s protein-making machinery, and overall protein synthesis. We showed that the synthetic compound had a more potent effect on this process than the natural signal.

This is a critical finding because it demonstrates that while synthetic drugs can mimic a specific action within a cell, they may also have other, unintended effects. This knowledge is vital for understanding the therapeutic potential and potential side effects of these types of drugs.

For more information, please see the full publication here.