Protein Kinase C is NOT Oncogenic! Protein Kinase C (PKC) is a group of enzymes that act as catalysts for a host of cellular functions, among which are cancer-relevant activities, such as cell survival, proliferation, apoptosis, and migration. The discovery that they are receptors for tumor-producing phorbol esters, plant-derived compounds that bind to and activate PKC, created a dogma that activation of PKCs by phorbol esters promoted carcinogen-induced tumorigenesis. For three decades, researchers have sought to find new cancer therapies based on the idea that inhibiting or blocking PKC signals would hinder or halt tumor development, said Alexandra Newton, PhD, professor of pharmacology and the studys principal investigator, but PKCs have remained an elusive chemotherapeutic target. Using live cell imaging, researchers, characterized 8 percent of the more than 550 PKC mutations identified in human cancers. This led to the unexpected discovery that the majority of mutations actually reduced or abolished PKC activity, and none were activating. The mutations impeded signal binding, prevented correct structuring of the enzyme, or impaired catalytic activity. When the scientists corrected a loss-of-function PKC mutation in the genome of a colon cancer cell line, tumor growth in a mouse model was reduced, demonstrating that normal PKC activity inhibits cancer. One possible explanation, said the researchers, is that PKC typically represses signaling from certain oncogenes - genes that can cause normal cells to become cancerous. When PKC is lost, oncogenic signaling increases, fueling tumor growth. The research is published in the journal Cell.
Posted on: Sun, 25 Jan 2015 09:16:00 +0000
Trending Topics
Recently Viewed Topics
© 2015