Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Regulation of cell proliferation is dependent on nucleocytoplasmic trafficking

24.08.2010
Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the Opioid Growth Factor (OGF, [Met5]-enkephalin) and its receptor, OGFr, a clinically important system with potent antitumor properties, has controlled entry from the cytoplasm to the nucleus.

The nucleocytoplasmic passage of OGF-OGFr is critical to cell proliferation and suggests that there are hierarchical levels of nuclear import. This discovery, reported in the September 2010 issue of Experimental Biology and Medicine, provides new insights into understanding the pathobiology of diseases related to this native biological system, and contributes to the development of new agents that will enhance treatment effectiveness.

Previous immunohistochemical and immunoelectron microscope studies have detected OGF and OGFr in both the cytoplasm and the nucleus. 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. Experiments utilizing a human cancer cell line, a squamous cell carcinoma of the head and neck, and a probe of OGFr fused to green fluorescent protein (eGFP), revealed the presence of a transport factor, karyopherin â, which plays a key role in nucleocytoplasmic transport. Moreover, directionality of transport for karyopherin â is dependent on the small guanosine triphophatase (GTPase) Ran. Knockdown of karyopherin â or Ran with siRNAs, but not the adaptor molecule karyopherin á, prevented transport of OGFr-eGFP and resulted in a marked increase in DNA synthesis. These results document that the pathway for regulating the cell cycle by 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, autoimmune diseases, and cancer."

Dr. Steve Goodman, Editor-in-Chief of Experimental Biology and Medicine stated "Ian Zagon and his colleagues are responsible for the describing the myriad of functions of the Opioid Growth Factor (OGF) and its receptor (OGFr) in health and disease. In this very interesting article, they have demonstrated the molecular mechanisms underlying nuclear import of OGF-OGFr. Specifically, they have demonstrated a role for karyopherin â and Ran in this process. The nuclear transport of OGF-OGFr is critical for the regulation of cell proliferation."

Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit www.ebmonline.org.

Dr. Ian Zagon | EurekAlert!
Further information:
http://www.psu.edu

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>