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Archive - Oct 16, 2012

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Cold Viruses Provide Clues to New Cancer Therapies

Cold viruses generally get a bad rap----which they've certainly earned----but new findings by a team of scientists at the Salk Institute for Biological Studies, and collaborators, suggest that these viruses might also be a valuable ally in the fight against cancer. Adenovirus, a type of cold virus, has developed molecular tools----proteins----that allow it to hijack a cell's molecular machinery, including large cellular machines involved in growth, replication, and cancer suppression. The Salk scientists identified the construction of these molecular weapons and found that they bind together into long chains (polymers) to form a three-dimensional web inside cells that traps and overpowers cellular sentries involved in growth and cancer suppression. The findings, published in the October 12, 2012 issue of Cell, suggest a new avenue for developing cancer therapies by mimicking the strategies employed by the viruses. "Cancer was once a black box," says Dr. Clodagh O'Shea, an assistant professor in Salk's Molecular and Cell Biology Laboratory, who led the study. "The key that opened that box was revealing the interactions between small DNA tumor virus proteins and cellular tumor suppressor complexes. But without knowing the structure of the proteins they use to attack cells, we were at a loss for how these tiny weapons win out over much larger tumor suppressors." Dr. O'Shea's team studied E4-ORF3, a cancer-causing protein encoded by adenovirus, which prevents the p53 tumor suppressor protein from binding to its target genes. Known as the "guardian of the genome," p53 normally suppresses tumors by causing cells with DNA damage----a hallmark of cancer----to self-destruct.