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Regulation of cell proliferation by the OGF-OGFr axis is dependent on nuclear localization signals
Date:4/22/2009

GF-OGFr complex involves the shuttling of the peptide-receptor complex from the cytoplasm to the nucleus, as well as transport receptors.

The research team was comprised of Dr. Ian S. Zagon, Distinguished University Professor, and Dr. Patricia J. McLaughlin, Professor, along with a postdoctoral fellow Dr. Fan Cheng, in the Department of Neural & Behavioral Sciences. Drs. Zagon and McLaughlin discovered the growth related activity of endogenous opioids, identified OGF as the specific peptide, cloned and sequenced OGFr, and collaborated on demonstrating the remarkable properties of these native peptides in a variety of clinical studies. OGF has proven successful in a Phase I clinical, trial, and Phase II trials for pancreatic cancer and squamous cell carcinoma of the head and neck are in progress. Co-author Dr. McLaughlin states: "Given the extraordinary biological control of the cell cycle by the OGF-OGFr axis, it may be envisioned that either a loss or a gain in transport shuttling pathways could contribute to the onset and progression of disease." Dr. Zagon adds that "The clinical implications of the study speak to whether changes in nucleocytoplasmic machinery related to the OGF-OGFr axis, part of the body's own machinery governing physiological processes, may be involved with understanding the etiology and pathogenesis of human disease, as well as the basis for the treatment of human disorders."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Zagon and colleagues have discovered that the Opioid Growth Factor (OGF, [Met5]-enkephalin), a clinically important antitumor agent, is dependent on shuttling of the peptide and the OGF receptor from the cytoplasm to the nucleus. This discovery may provide valuable information to understanding the etiology and pathogenesis of diseases related to this native biological system, as well as to development of new agents that will enhance treatment effectiveness". <
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Contact: Dr. Ian S. Zagon
isz1@psu.edu
717-531-6409
Society for Experimental Biology and Medicine
Source:Eurekalert

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