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

This release is available in Chinese.

Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the efficacy of the Opioid Growth Factor (OGF, [Met5]-enkephalin), a clinically important antitumor agent, is dependent on nucleocytoplasmic translocation and reliant on the integrity of nuclear localization signals in the OGF receptor (OGFr). This discovery, reported in the May 09 issue of Experimental Biology and Medicine, provides new insights into the mechanism of an important endogenous system that serves as a tonically active, constitutively expressed, inhibitory regulator of DNA synthesis. This valuable information not only may contribute to understanding the etiology and pathogenesis of diseases related to this native biological system, but to the development of new agents that will enhance effectiveness in treatment.

Previous immunohistochemical and immunoelectron microscope studies have detected OGF and OGFr in both the cytoplasmic and the nuclear compartments. The OGF-OGFr axis is known to regulate cell proliferation by modulating cyclin dependent kinase inhibitors, resulting in a retardation of cells at the G1-S interface of the cell cycle. To address the question of the location and temporal relationships of OGFr nucleocytoplasmic trafficking, a probe of OGFr fused to green fluorescent protein (eGFP) was constructed. Experiments with a human cancer cell, a squamous cell carcinoma of the head and neck, revealed that translation of OGFr required approximately 5 hours, and transit into the nucleus took 8 hours; OGFr remained in the nucleus for up to 8 days. Transport through the nuclear pore and repression of cell proliferation required two of the three nuclear localization signals (NLS) in OGFr. These results show that the pathway for regulating the cell cycle by the OGF-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".


'/>"/>

Contact: Dr. Ian S. Zagon
isz1@psu.edu
717-531-6409
Society for Experimental Biology and Medicine
Source:Eurekalert

Related biology news :

1. A paradigm shift in immune response regulation
2. Unclear regulations obstacle to biological diversity
3. New edition of laboratory manual includes cutting-edge techniques to study gene regulation
4. Scientists shed light on evolution of gene regulation
5. Conaway Lab identifies novel mechanism for regulation of gene expression
6. CU-Boulder study suggests air quality regulations miss key pollutants
7. Carbon Disclosure Project: Worlds largest corporations seek clarity on climate change regulation
8. New insights into the regulation of PTEN tumor suppression function
9. New regulations tighten controls on restricted chemicals
10. Systems biology approach identifies nutrient regulation of biological clock in plants
11. Epigenetic regulation by the MMB/dREAM complex
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/4/2017)... LAS VEGAS , Jan. 4, 2017  For the thousands of ... , a global leader in connected health and biometric measurement devices and ... pressure monitors. On display in A&D Medical,s special CES ... monitors represent the ongoing expansion of the company,s WellnessConnected product ... ...
(Date:12/20/2016)... 2016 The rising popularity of mobility ... is stoking significant interest in keyless access systems. ... low energy (BLE), biometrics and near-field communication (NFC) ... of wireless technologies in the automotive industry. This ... access systems opens the market to specialist companies ...
(Date:12/16/2016)... NEW YORK , Dec. 16, 2016 The global ... reach USD 12.14 billion by 2021 from USD 5.31 billion in ... ... market is mainly driven by technological advancements in medical devices, launch ... devices, rising preference for wireless connectivity among healthcare providers, and increasing ...
Breaking Biology News(10 mins):
(Date:1/13/2017)... ... 13, 2017 , ... FireflySci has been busy rolling out ... diverse customer base. The latest entry in this field is a series of ... Bio-Rad. FireflySci is introducing three distinct varieties including a 10x1mm, 10x2 and 10x4 ...
(Date:1/12/2017)... , ... January 12, 2017 ... ... devices with short response times capable of performing routine electrochemical biosensing has ... screen-printed electrodes provide fast, sensitive detection and quantification of various analytes in ...
(Date:1/12/2017)... Jan. 12, 2017   Protein Sciences Corporation ... of Flublok Influenza Vaccine ®, announced today ... had good safety results and induced strong neutralizing ... The product is expected to advance into human ... addition, the Institute of Technology in Immunobiologicals of ...
(Date:1/11/2017)... ... January 11, 2017 , ... Phase 1 clinical trial data ... the investigational anti-cancer agent tucatinib (formerly ONT-380) against HER2+ breast cancer. The 50 ... of these heavily pretreated patients saw clinical benefit from the drug, with at ...
Breaking Biology Technology: