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Regulation of cell proliferation is dependent on nucleocytoplasmic trafficking
Date:8/23/2010

the OGF-OGFr axis involves the timely and faithful translocation of this peptide-receptor complex across the nuclear envelope. This nucleocytoplasmic trafficking is critical for cell proliferation.

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 cell proliferative properties of endogenous opioids, identified OGF as the specific opioid peptide involved, and cloned and sequenced OGFr. Along with Dr. Cheng, they have documented that OGF enters cells by clathrin-mediated endocytosis, showed that the OGF-OGFr complex undergoes nucleocytoplasmic trafficking which is dependent on nuclear localization signals, and collaborated on demonstrating the remarkable properties of these native peptides in a variety of clinical studies. OGF has proven successful in Phase I and Phase II clinical trials for pancreatic cancer, and safety and efficacy studies for squamous cell carcinoma of the head and neck, and hepatocellular carcinoma are in progress. Co-author Dr. McLaughlin states "Given the extraordinary multifaceted and subtle biological control of the cell cycle by the OGF-OGFr axis, it may be envisioned that either a loss or a gain in nucleocytoplasmic transport could contribute to the onset and progression of disease. Localization of these proteins in the wrong cellular compartments could result in pathological states. " Dr. Zagon adds that "The clinical implications of the study speak to whether changes in factors related to the nucleocytoplasmic pathway of the OGF-OGFr axis, part of the body's own machinery governing physiological processes, can be mobilized in treatment of human disorders. Enhancement of these elements could prove extremely effective in reducing abnormal responses associated with cell proliferation as in inflammation, aut
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Contact: Dr. Ian Zagon
isz1@psu.edu
717-531-8650
Society for Experimental Biology and Medicine
Source:Eurekalert

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