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Tiny Worm Reveals Workings Of Suspected Tumor Protein

Harvard Medical School Researchers Link Viral Oncogenesis and Cell Differentiation in a Mystery Protein of the Nematode C. Elegans

BOSTON--March 27, 1998--The tiny worm that has become a darling of developmental biologists has revealed a biological function for a mysterious protein that may play a role in the growth of tumors.

In the cover article of the April 1 Genes and Development, Yang Shi, HMS associate professor of pathology, reports that the worm's version of the human protein p300 helps cells in the early embryo decide what kind of tissue to become. Shi found that p300 also is critical for determining the number of cells formed in the embryo. His finding validates earlier cell culture experiments on how viral cancer-causing proteins subvert a cell's growth.

For the first time, the study demonstrates what p300 does in a live organism. It also suggests a mechanism for how the protein might work, forging a link to histone acetylation, an area of research that has produced major advances in the past 2 years.

The paper is an example of how unlikely creatures, such as the fruit fly, the frog, or the nematode Caenorhabditis elegans, offer shortcuts toward understanding human biology. When researchers realized that many human genes exist and function in similar forms in most species--half of all human genes are estimated to have a correlate in C. elegans, for example--they decided to exploit the superior methods of genetic analysis available for simpler animals.

Shi joined the worm community because of his interest in viral oncogenesis. From earlier work, he knew that the adenovirus oncoprotein E1A disables the host protein p300. This interaction is key to E1A's ability to make a normal cell cancerous; it prevents immature cells from differentiating into mature ones.

To determine the role of p300, Shi collaborated with co-author Craig Mello of the University of Massachu
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Contact: Peta Gillyatt
pgillyat@warren.med.harvard.edu
617-432-0443
Harvard Medical School
31-Mar-1998


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