A natural tumor suppressor that could potentially be turned on in certain cancer cells to prevent the formation of tumors has been discovered by researchers at the University of California, San Diego (UCSD) School of Medicine.
Akt/protein kinase B controls the balance between cell survival and cell death. The activated form of this kinase tips the balance towards cell proliferation and survival, whereas the inactive form tips the balance towards programmed cell death, apoptosis. Akt can be inactivated by two mechanisms: the tumor suppressor PTEN pre-empts activation by removing the activating signals, and the tumor suppressor PHLPP terminates activation by directly turning off a key phosphorylation switch on Akt.
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 studys 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."
Sue Pondrom | EurekAlert!
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