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Scientists discover a mechanism that can send cells on the road to cancer
Date:4/22/2008

proteins adenovirus codes for -- proteins like E1A -- we are tapping into a kind of natural growth-control mechanism.

The utility of DNA tumor viruses for cancer research is based on the premise that theyve evolved to target the minimum number of cellular pathways necessary for virus propagation, said Dr. Lowe. When things go awry, understanding how a tumor virus like adenovirus promotes cancer can reveal, in turn, the most vulnerable pathways and nodes that are linked to tumorigenesis, Dr. Hannon added.

Commandeering the Cell Cycle

Because a tumor virus needs to commandeer the reproductive machinery of a living cell to survive, it must force the host cell to enter the reproductive, or S-phase, of its cycle. Past research has demonstrated that a protein called E2F is central in the process by which S-phase is activated. When the cell is not reproducing, E2F is known to be inhibited by its binding to another protein, called Rb, or retinoblastoma protein.

Its this regulated association of E2F and Rb that is one of the primary mechanisms through which cells normally progress into S-phase, Dr. Tansey said. The E1A protein, after binding Rb, is capable of physically pulling it off the E2F molecule. This unleashes the cell to replicate its DNA. And this, in turn, can promote transformations associated with cancer.

Recently, its been shown that E1As cancer-promoting activity is more extensive, also involving a gene-regulating protein called p400. Until the CSHL/Stony Brook team published its current paper, no one knew how E1As binding with p400 affected the process.

E1As Role in Another Oncogenic Pathway

The team knew from prior studies that when the E1A and p400 proteins were bound to one another, cellular growth control was disrupted. The question was why this potentially oncogenic effect occurred. What mechanisms were set in motion by the binding of these two proteins?

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Contact: Jim Bono
bono@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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