A paper published in the online edition of Current Biology reports that a graduate student from Simon Fraser University and her thesis supervisor discovered how a certain protein type controls the growth of another protein. The discovery could contribute to research in the fight against cancer.
Esther Verheyen, an SFU professor of molecular biology and biochemistry, and her Master’s of Science student Joanna Chen managed to reveal how Hipk, a protein kinase, can be manipulated to stop Yorkie, a protein that leads to overgrowth of cell tissue in eyes, legs and wings of flies, from causing tissue overgrowth in flies.
Hipk is an enzyme which deposits a phosphate residue on other proteins to control their activity, whilst the Yorkie protein, also known as ‘Yap’ in humans, causes overgrowth of cell tissue in the eyes, legs and wings of flies. Human tumors often contain high levels of Yap.
During experiments on Drosophila (fruit flies), the team discovered that Hipk was able to cause overgrowths, which were comparable with those found on tissue with too much Yorkie. The team then genetically modified the flies so that their normal organ and limb tissue contained a higher concentration of Yorkie and a lower concentration of Hipk.
Chen comments: “When we did that. Yorkie could not cause overgrowths anymore. We were able to show this need for Hipk to be present in a number of different fly tissues, such as the eyes, legs and wings.”
Verheyen continued:
“We found that Hipk could add a phosphate residue on Yorkie and we thought this might explain how Hipk could disrupt Yorkie’s ability to cause an overgrowth. This is a very common and reversible method of regulating protein activity, and, as a result, many essential developmental processes.
Next we tested a mutant form of Hipk that had lost its ability to add phosphates to Yorkie. This form of Hipk could no longer prompt Yorkie to trigger cell proliferation or do anything to regulate cell growth. Hipk is the first discovery of a protein kinase that regulates Yorkie by stimulating its cell proliferation ability. All other known protein kinases either directly inhibit or block Yorkie from working.”
According to Verheyen and Chen, the discovery is causing great excitement in the molecular biology science community. Chen who graduated in June, and who will be working as a research assistant at the Vancouver Prostate Centre in August, explains:
“We have identified a factor that in flies is required for even overly active Yorkie to trigger overgrowth. By analogy, perhaps the human form of Hipk is needed in cells for overly active Yap (human form of Yorkie) to induce tumors. So if we can inhibit or reduce Hipk activity, it would allow us to prevent overgrowths and possibly cancer caused by excessive Yap in humans.”
The team is now investigating whether their newly discovered cell growth regulation mechanism occurs amongst different species, like mice, since mice have similar Hipk proteins as humans.
Written by Petra Rattue