January 1, 2019

Researchers at the UNC Gillings School of Global Public Health have identified a molecule that activates and increases the function of the p53 tumor-suppressor protein, which could lead to more novel and targeted approaches to cancer treatment.

The results, “C16-ceramide is a natural regulatory ligand of p53 in cellular stress response,” were published online in Nature Communications on October 8, 2018.

Dr. Natalia Krupenko

Dr. Natalia Krupenko

Natalia Krupenko, PhD, assistant professor of nutrition at the Gillings School, is lead author on the paper. Sergey A. Krupenko, PhD, professor of nutrition, is a co-author. The research was performed at the University of North Carolina at Chapel Hill Nutrition Research Institute, in Kannapolis, N.C.

The team identified C16-ceramide as a ligand – a molecule that binds to a protein and impacts its function ¬– of the p53 protein, which is a known tumor suppressor. Under normal conditions in nonstressed cells, p53 is a short-lived protein that is bound by MDM2, another negative regulator of p53, and is marked for degradation.

The ceramide’s impact on this process is that it increases the life of the p53 protein, enabling it to remain stable longer and cause more of the tumor cells to be destroyed. The team also found that a deficiency in the vitamin folate places a stress on the cellular activity that triggers the body’s production of this vital ligand, leading to a more effective function of the p53.

Natalia Krupenko’s research has focused on the role of folate in health and disease. She said the team’s discovery is a major step toward understanding how cells work to maintain the body’s normal function.

“Human cells have many regulatory proteins that help coordinate their biochemical reactions in ways that support cellular functions, survival, and responses to changing conditions outside the cells,” she said. “The p53 protein is one of the most studied cellular regulators, as research has shown the gene to be mutated in more than half of all cancers. Because of this, many laboratories are investigating how to ‘fix’ the ‘defective’ p53 or find a way to overcome its dysfunction.”

Krupenko said that understanding the biological and cellular processes that help prevent or eradicate this deadly disease has a potential to improve public health.

“Cancer is a public health issue,” she said. “Development of novel therapeutic approaches to treat cancer and approaches for cancer prevention are instrumental in improving public health.”


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