PROVIDENCE, R.I. [Brown University] If the fight against breast cancer were a criminal investigation, then the proteins survivin, HDAC6, CBP, and CRM1 would be among the shadier figures. In that vein, a study to be published in the March 30 Journal of Biological Chemistry is the police report that reveals a key moment for keeping cancer cells alive: survivin's jailbreak from the nucleus, aided and abetted by the other proteins. The research highlights that a protein's location in a cell affects its impact on disease, and offers clear new leads for the investigation.
All four proteins were already under suspicion. Researchers, for example, have already tried to assess what levels of HDAC6 in patients with estrogen-receptor positive breast cancer may mean for their prognosis. The results have been inconclusive. The new research suggests that measuring overall levels may not be enough, said the study's senior author Dr. Rachel Altura, associate professor of pediatrics in The Warren Alpert Medical School of Brown University and a pediatric oncologist at Hasbro Children's Hospital.
"We need to look not only at the levels, but also where is it in the cell," she said.
Altura's emphasis on location comes from what her research team found as they tracked and tweaked the comings and goings of survivin in cells. Inside the nucleus, survivin is no problem. Outside the nucleus, but within the cell, it can prevent normal cell death, allowing cancer cells to persist.
In previous work, Altura and her collaborators established that under normal circumstances, CBP chemically regulates survivin, a process called acetylation, and keeps it in the nucleus. The question in the new work was how survivin gets out.
In a series of experiments, what they observed was that in human and mouse breast cancer cells, HDAC6 gathers at the boundary between the nucleus and the rest of the cell, becomes activated by CBP, then binds survivin a
|Contact: David Orenstein|