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

Flipping the 'Off' Switch on Cell Growth

Published: Wednesday, February 27, 2013
Last Updated: Wednesday, February 27, 2013
Bookmark and Share
Protein uses multiple means to help cells cope when oxygen runs low.

A protein known for turning on genes to help cells survive low-oxygen conditions also slows down the copying of new DNA strands, thus shutting down the growth of new cells, Johns Hopkins researchers report. Their discovery has wide-ranging implications, they say, given the importance of this copying — known as DNA replication — and new cell growth to many of the body’s functions and in such diseases as cancer.

“We’ve long known that this protein, HIF-1alpha, can switch hundreds of genes on or off in response to low oxygen conditions,” says Gregg Semenza, M.D., Ph.D., a molecular biologist who led the research team and has long studied the role of low-oxygen conditions in cancer, lung disease and heart disorders. “We’ve now learned that HIF-1alpha is even more versatile than we thought, as it can work directly to stop new cells from forming.” A report on the discovery appears in the Feb. 12 issue of Science Signaling.

With his team, Semenza, who is the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine’s Institute for Cell Engineering and McKusick-Nathans Institute of Genetic Medicine, discovered HIF-1alpha in the 1990s and has studied it ever since, pinpointing a multitude of genes in different types of cells that have their activity ramped up or down by the activated protein. These changes in so-called “gene expression” help cells survive when oxygen-rich blood flow to an area slows or stops temporarily; they also allow tumors to build new blood vessels to feed themselves.

To learn how HIF-1alpha’s own activity is controlled, the team looked for proteins from human cells that would attach to HIF-1alpha. They found two, MCM3 and MCM7, that limited HIF-1alpha’s activity, and were also part of the DNA replication machinery. Those results were reported in 2011.

In the new research, Semenza and his colleagues further probed HIF-1alpha’s relationship to DNA replication by comparing cells in low-oxygen conditions to cells kept under normal conditions. They measured the amount of DNA replication complexes in the cells, as well as how active the complexes were. The cells kept in low-oxygen conditions, which had stopped dividing, had just as much of the DNA replication machinery as the normal dividing cells, the researchers found; the difference was that the machinery wasn’t working. It turned out that in the nondividing cells, HIF-1alpha was binding to a protein that loads the DNA replication complex onto DNA strands, and preventing the complex from being activated.

“Our experiments answered the long-standing question of how, exactly, cells stop dividing in response to low oxygen,” says Maimon Hubbi, Ph.D., a member of Semenza’s team who is now working toward an M.D. degree. “It also shows us that the relationship between HIF-1alpha and the DNA replication complex is reciprocal — that is, each can shut the other down.”

Other authors on the report are Kshitiz, Daniele M. Gilkes, Sergio Rey, Carmen C. Wong, Weibo Luo and Andre Levchenko, all of the Johns Hopkins University School of Medicine, Deok-Ho Kim of the University of Washington, Seattle and Chi V. Dang of the University of Pennsylvania.


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 3,300+ scientific posters on ePosters
  • More than 4,800+ 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

Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Wednesday, July 20, 2016
Seeing Through HIV's Disguises
Researchers identify 25 human proteins that may be crucial for HIV-1 infection and survival.
Friday, March 01, 2013
Phase I Trial Commences Treating Patients with Pancreatic and Colorectal Cancer Using Monoclonal Antibody
Pre-clinical studies have demonstrated that NPC-1 specifically targets pancreatic and colorectal cancer sparing healthy tissue.
Wednesday, February 10, 2010
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
New Centre Offers Ultra-Speed Protein Analysis
UW-Madison researchers to establish development centre for next-gen protein measurement technologies.
Protein Nanocages Could Improve Drug Design and Delivery
HHMI scientists have designed and built 10 large protein icosahedra that are similar to viral capsids that carry viral DNA.
Virus Inspired Cell Cargo Ships
Virus-inspired container design may lead to cell cargo ships following construction of ten large, two-component, icosahedral protein complexes.
Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Structure of Cold Virus Solved
Researchers have identified the structure of an elusive cold virus linked to child asthma and respiratory infections, providing the foundation for treating the virus.
New Protein Model Could Accelerate Drug Development
Stony Brook-led international research team creates ultra-fast approach to model protein interactions.
Researchers Can Control Genes Involved in Cancer
A new way to control the activity of a protein, that is often upregulated in cancer, has been discovered by Moffitt researchers through monoubiquitination mechanism.
Mitochondrial Role in Metastatic Cancer
Researchers have manipulated proteins, sourced from tumour cells, that are essential for maintaining tumour cells and in doing so, have significantly reduced the ability of cancer cells.
Liquid Biopsy Predicts Colon Cancer Recurrence
Scientists have used a genetic test that spots bits of cancer-related DNA circulating in the blood to accurately predict the likelihood of the disease’s return in some — but not all — of a small group of patients with early-stage colon cancer.
Scroll Up
Scroll Down
SELECTBIO

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!