Three Phosphatases Regulate Activity of Key Oncogene

In the current paper, published in the September 2008 issue of the journal Molecular Cell, they identified the phosphatases PDXP, PP1, and PP2A as key negative regulators of SRC-3 activity.

PDXP and PP2A were found to remove phosphate from SRC-3 and inhibit its ligand-dependent association with estrogen receptor. PP1 stabilized SRC-3 protein by blocking its proteasome-dependent turnover through dephosphorylation of two previously unidentified phosphorylation sites required for activity. These two sites were primary determinants of SRC-3 turnover. Moreover, PP1 regulated the oncogenic cell proliferation and invasion functions of SRC-3 in breast cancer cells.

"This kind of information provides a target for the production of drugs against cancer,” said senior author Dr. Bert O'Malley, professor of molecular and cellular biology at Baylor College of Medicine. "One can already find drugs that stimulate or inhibit phosphatases in other disease processes. In cancer right now, many drugs work the same way. They are toxic to all cells. Because the cancer cell grows faster, the drug is more toxic, but there is nothing selective about the process. In the past decade, we have realized that there has to be a better, more intellectual approach to cancer. In fact, some already exist.”

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