Scientists solve structure of gene regulator that plays key role...( (PHILADELPHIA) Scientists at The Wi...),Health

(PHILADELPHIA) Scientists at The Wistar Institute have collaborated on a major advance in understanding a gene regulator that contributes to some of the deadliest cancers in humans. The culmination of 10 years work, their research paves the way for the development of new cancer therapies.

During much of its lifetime, the DNA that resides in each of our cells exists in an inactive form, stored inside densely knotted structures in the cell nucleus. There, the DNA is wound spool-like around proteins called histones, which bind to and restrict the DNAs activity. For a cell to activate a gene, many proteins, called transcription factors, work in concert to separate DNA from the histones. One family of transcription factors are enzymes known as HATs, or histone acetyltransferases, which transfer acetate groups onto the histones.

Wistar scientists, collaborating with researchers at the Johns Hopkins University School of Medicine, have made a major advance in the understanding of the structure and function of a key HAT enzyme called p300/CBP.

Unlike most HATs, which regulate the expression of only a few genes, p300/CBP is involved in the activation of a wide variety of genes. In addition, 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 anti-cancer drugs, says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and a senior author and corresponding author on the study. Philip A. Cole at Johns Hopkins is also a senior author and corresponding author.

Its unusual to have a HAT thats so implicated in cancer, and even more unusual to have one
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