One example of proteases making a positive difference is in connection with wound healing. When tissue is damaged, a molecular mechanism starts whereby a protease cleaves and activates the next protease, which then cleaves and activates a third protease, and so on. In other words, it sets off a repair mechanism a kind of domino effect whereby a single protease can issue a small signal to a whole string of proteases. However, this mechanism can also be exploited by cancer cells, enabling them to spread.
"My generation of molecular biologists learned that proteases are enzymes which are capable of cleaving and activating other proteases, and that this molecular mechanism called proteolysis is their sole function. However, our new research findings show that proteases have functions which until now have been overlooked. Yet the key to designing effective drugs is to understand all the molecular mechanisms that make the cancer grow," says Stine Friis.
Bind instead of cleave
More specifically, the research group has worked with two proteases, matriptase and prostasin, which are both essential for maintaining healthy cells in the skin, intestines and other organs. However, in contrast to what has so far been believed, the two proteases do not activate one another by one cleaving the next, i.e. through proteolysis. In fact, prostasin's role in activating matriptase is surprisingly independent of this mechanism. Instead of cleaving one another, the two proteases bind to each other, which is most unusual, and thereby start important processes.
Through knowing about this previously overseen but vital function of how proteases activate the cell's signals, researchers hope to improve our understanding of how proteases operate in the body. And not just in normal circumstances, but also in situations where something malfunctions with the protease balance, such as in cancer.
"Hopefully our new findings will inspire o
|Contact: Stine Friis|
University of Copenhagen