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Study may help clarify how cells grow

CHAPEL HILL - A study led by a University of North Carolina scientist sheds new light on the process of cell growth regulation. The study, which focuses on the complex network of biochemical signals between proteins and enzymes within cells, helps clarify how those signals initiate or limit cell growth.

Although still too basic for clinical use, the findings suggest the possibility of new drugs that would target specific growth-inducing molecules within cancer cells.

A report of the study appears in the January 20 issue of the science journal Nature.

According to Lee Graves, Ph.D., assistant professor of pharmacology at UNC School of Medicine in Chapel Hill and the study's principal investigator, the enzyme MAP kinase (MAPK) is a key component of a signaling pathway initiated by growth factors.

"This is just one of many signaling pathways but we know it's essential for growth," he said. "So the key question has been, what are the specific targets of MAP kinase; that is, what are the important things it does, and how does it regulate cell growth?"

In their search for the answer, Graves and his study collaborators at UNC Lineberger Cancer Center and Wayne State University in Detroit, focused on an enzyme called carbamoyl phosphate synthetase, or CPS II. Deep within the cell's molecular machinery, this enzyme determines the rate of pyrimidine nucleotide biosynthesis, without which cell growth is impossible. Nucleotides are the building blocks of RNA and DNA synthesis. Consequently, blocking the synthesis of these molecules has been the strategy of numerous anti-cancer therapies. Normally, as cellular levels of pyrimidine nucleotides build up, CPS II is turned of by a process of 'feedback' inhibition, Graves explains. "What we think happens is that in response to a growth signal, MAP kinase attaches a phosphorous molecule to CPS II, thus preventing feedback inhibition and allowing cells to make more nucleotides."

The UNC pharmacologist point
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Contact: Leslie H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
19-Jan-2000


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