Gene Regulator Key to New Cancer Therapies

Philadelphia, PA (Feb. 13)-Scientists at the Wistar Institute are trying to understand a gene regulator that could lead them closer to developing new cancer therapies. A 10-year collaborative study with researchers at the Johns Hopkins University School of Medicine has focused on the structure and function of a key histone acetyltransferases (HAT) enzyme called p300/CBP.

HATs are one family of transcription factors, which are proteins that separate DNA from histones, and increase the activity of DNA. The p300/CBP is in involved in wide variety of genes, more than most other HATs.

“Aberrant p300/CBP activity contributes to pancreatic, colon, and lung cancer-among the deadliest cancers in humans-as well as gastric and thyroid cancer and some leukemias. In addition to acting as an oncoprotein by promoting tumors, p300/CBP also can suppress tumors. These unusual properties have made p300/CBP one of the most studied enzymes in the HAT family, and a target for developing new anticancer drugs,” says Ronen Marmorstein, PhD, a professor in the gene expression and regulation program at Wistar.

The researchers also worked to understand the three-dimensional structure of the p300/CBP HAT segment that inhibits the activity of tumors and oncoprotein activity. The research reveals how the binding site and chemical mechanism of the enzyme enable it to regulate various genes.

The full study is published in the Feb. 14 issue of Nature.