From “Paper of the Week” to “Breast Cancer Treatment of the Year”?

How a Calcium-binding Protein Activates an Estrogen Receptor

by heather dolan

David B. Sacks is a celebrity . . . in the chemistry world, that is. One of his studies has been designated “Paper of the Week” in the March 16 issue of Journal of Biological Chemistry. Each year, only 50 to 100 papers are selected for this honor out of more than 6,600 published.

Sacks, along with research fellow Zhigang Li and University of California at Davis colleagues James B. Ames and Yonghong Zhang, are being recognized for their work on how the calcium-binding protein calmodulin (CaM) activates an estrogen receptor (ER) implicated in breast cancer. (J Biol Chem 287:9336-9344, 2012)

About 70 percent of breast cancers depend on ERs for growth. The researchers described how the structure of CaM induces ER-alpha dimerization, the linkage of two molecules to form a single molecule, and prevents ER-alpha degradation.

These activities make CaM “unique among the known structures of calmodulin target complexes,” said Sacks, who is chief of the NIH Clinical Center’s Chemistry Service. Still, he was surprised that the study was highlighted in the journal. “I’ve previously published 35 papers in JBC and this is the first that was awarded ‘Paper of the Week.’”

Prior work done by Sacks’s group and others demonstrated that CaM inhibition reduces the growth of human breast-cancer cells. Sacks’s findings suggest that CaM is an important component of ER-signaling pathways, and that the molecular interaction between CaM and ER has the potential to be a therapeutic target for treating breast-cancer patients.

Although Sacks is pleased with the Journal of Biological Chemistry recognition, he knows there’s a lot of work ahead. “We continue to work on this exciting area of research,” he said, “and hope to generate further understanding of ER function.”