Breakthrough Anti-Cancer Mechanism Could Lead to a New Drug Strategy for this Disease
A fundamental discovery of the vital triggers of a cancer-blocking mechanism in cells could lead to the creation of a new treatment strategy for this disease.
Researchers at the Scripps Research Institute have found that certain enzymes can initiate a mechanism known as ‘oncogene-induced senescence’, which can block most cancer forms. This mechanism is mostly experienced when incipient skin cancers are transformed into slow growing moles.
In this new study, published in the journal Molecular Cell, these scientists demonstrates how key enzymes such as PRAK, Tip60 and p38 interact to create this mechanism. By forcing the activation of this cancer-blocking mechanism, these researchers could help create new cancer strategies, informed by better knowledge of the signalling pathway.
Associate professor in TSRI’s Department of Cell and Molecular Biology Peiqing Sun explains the need for this study as he says, “We have known about some of the molecular signals that mediate this senescence response, but we’ve needed to understand the signalling pathway in much more detail.”
About 10 years ago, Sun and his colleagues found that p38 is present at the top of the pathway for this mechanism while in 2007, it was discovered that this same enzyme also activating another known as PRAK. This research was conducted to understand further details of PRAK’s role in this pathway.
This detailed investigation was started by research associate Hui Zheng who began his search for binding partners of PRAK. Through a number of protein-interaction tests, Zheng discovered that the enzyme Tip60 forms a close connection with PRAK. Further experimentation indicated that this cancer-blocking mechanism only occurs when Tip60 is present and it acts on the PRAK enzyme by modifying it, through the addition of acetyl groups.
As Zheng says, the main PRAK enzyme needs two triggers in order to function: “Our tests showed that Tip60 binds to PRAK and acetylates it at a certain location, which helps activate PRAK. First the phosphorylation by p38 and then the acetylation by Tip60 are required for fully activating PRAK in this senescence–induction cascade.”
Oncogenes are developed through DNA damage, inherited mutations or another cause that drive cells to keep dividing beyond the traditional limits. Further tests do need to be done on this mechanism but, if scientists can discover a way to replicate this genetic formation in different kinds of individuals, they will be closer to producing the first cancer treatment that improves the longevity of life, without the side effects.
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