Located on chromosome 18 and called PH domain Leucine-rich repeat Protein Phosphatase (PHLPP, pronounced "flip"), the tumor suppressor is described in the April 1, 2005 issue of the journal Molecular Cell. The scientists demonstrated that PHLPP deletes a phosphate molecule, causing termination of cell-growth signaling by a protein called Akt that controls the balance between cell growth leading to cancer and cell death that prevents tumor formation.
"A drug that turns on PHLPP, so that it suppresses cell growth caused by Akt, could be a potential cancer therapy," said the study's senior author, Alexandra C. Newton, Ph.D., UCSD professor of pharmacology. "Currently there are no compounds identified to directly stop Akt from causing cancer growth, once Akt signaling has been initiated."
Scientists have known that Akt is critical in regulating cell growth and death, and that it is linked to some of the most common human cancers. Although one group of scientists discovered a molecule called PTEN*, which prevents activation of Akt, no one to date had determined how to directly turn off Akt once it has been activated.
Since the Akt molecule is locked in the "on" position when it has phosphate on it, the UCSD team reasoned that there must be another molecule that will strip off the phosphate and lock Akt in the "off" position. The scientists conducted a database search of the human genome for a phosphatase, which is an enzyme that acts as a catalyst in regulating cellular processes by removing phosphate molecules. Based on the chemical components of Akt, they specifically looked for a phosphatase linked to the PH domain, a protein module found in a wide variety of chemical signaling proteins in organisms r
Contact: Sue Pondrom
University of California - San Diego