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Newswise – TROY, NY – An antioxidant found in green tea may increase levels of p53, a naturally occurring anti-cancer protein known as the “guardian of the genome” for its ability to repair DNA damage or destroy cancer cells . Posted today in Nature communications, a study of the direct interaction between p53 and the green tea compound, epigallocatechin gallate (EGCG), points to a new target for the discovery of anticancer drugs.
“The p53 and EGCG molecules are extremely interesting. Mutations in p53 are found in over 50% of human cancers, while EGCG is the main antioxidant in green tea, a popular beverage around the world, ”said Chunyu Wang, corresponding author and professor of biological sciences at Rensselaer Polytechnic Institute. “We are now seeing that there is a previously unknown direct interaction between the two, which points to a new avenue for the development of anti-cancer drugs. Our work helps explain how EGCG is able to stimulate the anticancer activity of p53, opening the door to the development of drugs containing compounds similar to EGCG.
Wang, a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, is an expert in the use of nuclear magnetic resonance spectroscopy to study the specific mechanisms of Alzheimer’s disease and cancer, including p53, which he described it as “arguably the most important protein in human cancer.” “
P53 has several well-known anticancer functions, including stopping cell growth to allow DNA repair, activating DNA repair, and triggering programmed cell death – called apoptosis – if the DNA damage cannot be repaired. One end of the protein, known as the N-terminal domain, has a flexible shape and can therefore potentially perform multiple functions depending on its interaction with multiple molecules.
EGCG is a natural antioxidant, which means that it helps repair the almost constant damage done during oxygen metabolism. Found abundantly in green tea, EGCG is also packaged as an herbal supplement.
Wang’s team found that the interaction between EGCG and p53 preserves the protein against degradation. Typically, after being produced in the body, p53 is rapidly degraded when the N-terminal domain interacts with a protein called MDM2. This steady cycle of production and degradation keeps p53 levels low and constant.
“EGCG and MDM2 bind in the same place on p53, the N-terminal domain, so EGCG competes with MDM2,” Wang said. “When EGCG binds to p53, the protein is not degraded by MDM2, so the level of p53 will increase with the direct interaction with EGCG, and this means that there is more p53 for anticancer function. It’s a very important interaction. “
“By developing an understanding of the mechanisms at the molecular level that control key biochemical interactions linked to devastating diseases such as cancer and Alzheimer’s disease, Chunyu’s research lays the foundation for new and successful therapies,” said Curt Breneman , dean of the Rensselaer School of Science.
“EGCG binds the intrinsically disordered N-terminal domain of p53 and disrupts the p53-MDM2 interactionWas published with the support of several grants from the National Institutes of Health. At Rensselaer, Wang was joined in the research by Lauren Gandy, Weihua Jin, Lufeng Yan, Xinyue Liu, and Yuanyuan Xiao. The first author Jing Zhao is a former member of Wang’s lab, now at the faculty of China Agricultural University in Beijing, China. Co-first author Alan Blaney is a medical doctor. student at Upstate Medical University. Researchers also contributed from SUNY Upstate Medical Center; the University of Massachusetts, Amherst; New York University; the State University of New York at Binghamton; NYU Shanghai; and Merck Research Laboratories.
The authors also wished to acknowledge the broad collaboration that produced this research, including collaborations with Professors Stewart Loh and Michael Cosgrove of Upstate Medical University, Sozanne Solmaz of Binghamton University, Jianhan Chen of the University of Massachusetts, Amherst, Yingkai Zhang from NYU and David Ban, a Rensselaer alumnus who once worked as an undergraduate researcher in Wang’s lab, now a senior researcher at Merck.
About the Rensselaer Polytechnic Institute
Founded in 1824, the Rensselaer Polytechnic Institute is the first American university for technological research. Rensselaer comprises five schools, 32 research centers, over 145 academic programs and a vibrant community of over 7,900 students and over 100,000 living alumni. Rensselaer’s faculty and alumni include more than 145 National Academy members, six National Inventors Hall of Fame members, six National Medal of Technology winners, five National Science Medal winners and a Nobel Prize in physics. With almost 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on solving global challenges with a spirit of ingenuity and collaboration. To learn more, please visit www.rpi.edu.
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