Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research suggests molecular 'switch' may play role in tumor suppression

14.01.2013
Newly published research by Indiana University structural biologist Joel Ybe and colleagues identifies a "topology switch" in the protein clathrin, the function of which may shed light on molecular processes involved in tumor suppression.

The paper, available in and featured on the front cover of the Jan. 16, 2013, issue of FEBS Letters, a journal of the Federation of European Biochemical Societies, could broaden scientists' understanding of the importance of clathrin and potentially lead to new strategies for controlling cancer.

"This is a totally unexpected but wonderful finding," Ybe said. "It has exciting implications for understanding the role that clathrin may play in the growth or suppression of tumors."

Ybe is a senior research scientist in the Department of Molecular and Cellular Biochemistry in the IU College of Arts and Sciences. Co-authors of the paper are postdoctoral researchers Sarah Fontaine and Xiaoyan Lin; IU chemist Todd Stone; Sanjay Mishra, formerly at IU and now at Vanderbilt University; and Jay Nix of Lawrence Berkeley National Laboratory.

Typically found in a three-legged form called a trimer, clathrin is best understood for its role in endocytosis, the process by which cells absorb proteins and other molecules. But recent research has suggested that clathrin in a one-legged form, or monomer, may have a role in suppressing tumors. Ybe and his team show how a "switch" in clathrin can be flipped to produce non-trimeric clathrin molecules.

"Clathrin is known to function as a trimer in receptor-mediated endocytosis, but the existence of the monomeric form and its role in tumor suppression is less well-accepted," said Alexandra Ainsztein, who oversees membrane trafficking grants at the National Institute of General Medical Sciences of the National Institutes of Health. "By providing evidence for a model in which a molecular shift de-trimerizes clathrin and changes its cellular distribution, this work will spur further research into unanticipated roles for this important molecule in healthy and diseased cells."

In endocytosis, trimeric clathrin molecules bind together to form molecular packages that allow other substances to enter cells. Several years ago, researchers in Japan published evidence that clathrin can also serve as an activator of the protein p53, a known tumor suppressor.

For the activation to take place, clathrin and p53 must both be present in the cell's nucleus. The catch is that clathrin molecules cannot penetrate the nucleus in their usual, three-legged form. To enter, the three-legged clathrin molecule must be altered or "de-trimerized."

Using X-ray crystallography, Ybe and his team discovered a "topology switch" in the clathrin molecule. They showed they could break the switch by mutating one key amino acid that is part of the switch. The result: Clathrin was "detrimerized"; three-legged molecules were broken into one-legged ones.

Experimenting with both cancer and non-cancer cells, the researchers found the three-legged clathrin only in the cytoplasm of the cells, not the nucleus. But with the "switch" broken, clathrin formed monomers and was also present in the nucleus, where it could potentially activate tumor suppression.

Ybe said the results point to the need for additional research to better understand the structure and function of clathrin and the role it plays in cellular processes, including those involved in cancer. With the clathrin "switch" identified, researchers can attempt to better understand how it can be activated, with the goal of developing new therapies for suppressing the growth of tumors. Ybe has a patent pending on the idea to use the mutated form of clathrin to stimulate the natural anti-cancer activities of human cells.

The finding developed from Ybe's research on the role of clathrin in Huntington's disease, a genetic disorder that causes neurological degeneration and is estimated to affect about 15,000 people in the U.S. The National Institutes of Health awarded the project a $1.2 million, four-year grant in 2009. The NIH grant number is R01GM064387.

The article is available online. To speak with Ybe, please contact Steve Hinnefeld, IU Communications, 812-856-3488 or slhinnef@indiana.edu

Steve Hinnefeld | EurekAlert!
Further information:
http://www.iu.edu

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | 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: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

A new dead zone in the Indian Ocean could impact future marine nutrient balance

06.12.2016 | Earth Sciences

Significantly more productivity in USP lasers

06.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>