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Researchers find a protein that controls cell growth

ulting in cancer. Dr. Pagano says that his laboratory plans to ascertain whether there are mutations in the gene encoding the APC protein that cause Skp2 to accumulate. (If APC were mutated, then the instructions for Skp2 degradation would be missing). If so, then perhaps drugs can be developed that counter these mutations in APC.

"An increase in the amount of Skp2 contributes to cancer development," says Dr. Pagano. "Since APC controls the cellular abundance of Skp2, we think that APC deregulation plays a role in the malignant transformation of cells. If we could find a way to decrease the levels of Skp2 or inhibit its activity -- possibly through manipulation of APC -- then we may be able to develop new cancer therapies."

The Warren, New Jersey-based biotechnology company Celgene Corp. has given Dr. Pagano's laboratory a grant to study the cellular function of some Skp2 homologs, which have similar sequences of amino acids, with the idea that this will lead to the identification of novel targets for cancer therapies. In addition, Dr. Pagano's lab and Celgene are collaborating on a project to screen for inhibitors of Skp2, and several inhibitors already have been identified.

The co-authors of the Nature study are Tarig Bashir, Ph.D.; N. Valerio Dorrello, M.D.; Virginia Amador, Ph.D.; and Daniele Guardavaccaro, Ph.D. They are all members of Dr. Pagano's laboratory.


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Contact: Pamela McDonnell
Pamela.McDonnell@med.nyu.edu
212-404-5555
New York University Medical Center and School of Medicine
10-Mar-2004


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