Navigation Links
Research suggests molecular 'switch' may play role in tumor suppression
Date:1/13/2013

BLOOMINGTON, Ind. -- 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.


'/>"/>

Contact: Steve Hinnefeld
slhinnef@iu.edu
812-856-3488
Indiana University
Source:Eurekalert

Related medicine news :

1. Canada In Vitro Diagnostics Market Analysis and Forecasts to 2017 in New Research Report at RnRMarketResearch.com
2. ZijaExtreme.com Researches Vitamin D Deficiency & Using a More Natural Approach
3. Spectacles Market - New Industry Research Report is Now Available for Pre Order at Transparency Market Research
4. Game-based economics research explains why we roll the dice on flu shots
5. Experts aim to redefine healthcare and research ethics
6. Heart Muscle Cells Regenerate in Kids, Research Shows
7. Research Reveals Which Learning Methods Get an A
8. Researchers use iPSCs to define optimal treatment for managing life-threatening arrhythmias
9. Dental Implants Market - New Industry Research Report is Now Available for Pre Order at Transparency Market Research
10. UT Arlington receives Grand Challenges Explorations grant for research in global health
11. Book co-authored by USF Nursing Dean named 2012 Nursing Research Book of the Year
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/12/2017)... , ... October 12, 2017 , ... The American College ... to Carol Friedman, PhD, FACMI, during the Opening Session of AMIA’s Annual Symposium in ... , In honor of Morris F. Collen, a pioneer in the field of medical ...
(Date:10/12/2017)... ANGELES (PRWEB) , ... October 12, 2017 , ... ... Parsa Mohebi Hair Restoration, has recently contributed a medical article to the newly ... on cosmetictown.com. Dr. Mohebi’s article spotlights the hair transplant procedure known as ...
(Date:10/12/2017)... , ... October 12, 2017 , ... On Saturday, October ... treadmill relay – Miles by Moonlight to raise money for the American Heart Association ... more. , Teams will work together to keep their treadmills moving for 5 ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... in property taxes a year. In some states—like New York, New Jersey, Massachusetts, ... contrast, many overseas retirement havens have extremely low property-tax rates, which contributes to ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... content management, presents its enhanced Pepper Flow promotional review platform at the ... Pepper Flow’s increased insight-driven capabilities help marketers streamline the medical, legal, and ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... FRISCO, Texas , Oct. 11, 2017 /PRNewswire/ ... healthcare services, has amplified its effort during National ... patients about hereditary cancer risks. ... Journal of Clinical Oncology calculated that more than ... to have inherited mutations in BRCA1 or BRCA2 and ...
(Date:10/7/2017)... , Oct. 6, 2017   Provista, a ... than $100 billion in purchasing power, today announced a ... information. The Newsroom is the online home ... trends, infographics, expert bios, news releases, slideshows and events. ... to a wealth of resources at their fingertips, viewers ...
(Date:10/4/2017)... 4, 2017 OBP Medical , ... medical devices, today announced regulatory approval from ... (or Agência Nacional de Vigilância Sanitária (ANVISA)) to ... surgical retractor with integrated LED light source and ... and exposure of a tissue pocket or cavity ...
Breaking Medicine Technology: