Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

IU Research Suggests Molecular ‘Switch’ May Play Role in Tumor Suppression

Published: Wednesday, January 16, 2013
Last Updated: Wednesday, January 16, 2013
Bookmark and Share
Newly published research by Indiana University 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.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,900+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Tuesday, November 24, 2015
Biomarker Predicting Transplant Complications May be Key to Treating Them
A protein that can be used to predict if a stem cell transplant patient will suffer severe complications may also be the key to preventing those complications, an international research team based at the Indiana University School of Medicine reported Wednesday.
Monday, October 12, 2015
Scientific News
Top 10 Life Science Innovations of 2016
2016 has seen the release of some truly innovative products. To help you digest these developments, The Scientist have listed their top picks for the year.
Largest Resource of Protein-Protein Interactions
Researchers have developed the largest ever database of protein-protein interactions.
Bright Red Fluorescent Protein Created
Scientists have created a bright red, fluorescent protein that could be used to track essential cellular processes.
Protein Self-Regulates Abundance
Researchers have uncovered how a protein, that plays a crucial role in embryonic stem cell renewal, is regulated.
'Lab on the Skin' for Sweat Analysis
Northwestern University researchers develop a low-cost wearable electronic device that collects and analyzes sweat for health monitoring.
Building Better Nanodiscs
Researchers have improved upon the design of nanodiscs that provide an unprecedented view of viral infection.
Breast Cancer Cells Starve for Cystine
Depriving triple negative breast cancer, a treatment-resistant form of breast cancer, of cystine results in cancer cell death.
Novel Urine Test to Predict High-Risk Cervical Cancer
Preliminary studies affirm accuracy and potential cost savings to screen for virus-caused malignancy.
Protein-Folding Gene Helps Heal Wounds
Researchers identified a protein that dramatically accelerates wound healing in animal models.
Crop Yield Gets Boost with Modified Genes
Researchers increase plant proteins that result in more efficient use of sunlight.
Scroll Up
Scroll Down
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!