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How one virus uses mimicry to replicate successfully
Date:10/31/2007

(PHILADELPHIA) Both viruses and cancers subvert the growth-control machinery in a cell to serve their own needs. According to a new study, at least one virus uses mimicry to gain access to that machinery.

A common target for both is a cell protein called the retinoblastoma protein, or pRb, which serves to block cell division when potentially cancer-causing gene mutations are present. First identified in pediatric tumors of the retina, this tumor suppressor protein has since been found to play a role in many other forms of cancer when disrupted.

A number of viruses produce proteins that specifically target pRb, and scientists have studied these viruses and their proteins closely to better understand how normal cells can turn cancerous. Among such viruses are the adenoviruses, which produce a protein called E1A that interferes with pRb and its ability to control unwanted cell division. Adenoviruses are not themselves cancer causing, but a better understanding of how they interact with pRb might well shed light on related mechanisms used by other viruses to trigger cancers. For example, a protein that is functionally equivalent to E1A from human papillomavirus, called E7, causes cervical cancer in the cells it infects.

Until now, investigators had been unable to obtain detailed information about how E1A disrupts the normal function of pRb. In a new study, however, featured on the cover of the November 1 issue of the journal Genes & Development, researchers at The Wistar Institute have solved the three-dimensional structure of a molecular complex of pRb and E1A, providing the first atomic view of the viral E1A protein in action.

The findings show that that E1A operates in a novel way, mimicking a normal cellular protein called E2F that ordinarily binds to pRb in a controlled and regulated fashion.

The structural similarities between E1A and E2F are surprising and striking, says Ronen Marmorstein, Ph.D., a professor in
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
Source:Eurekalert

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