Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Flipping the 'off' switch on cell growth

25.02.2013
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-1á, 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-1á 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 Institute for Genomic Medicine, discovered HIF-1á 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-1á's own activity is controlled, the team looked for proteins from human cells that would attach to HIF-1á. They found two, MCM3 and MCM7, that limited HIF-1á'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-1á'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-1á 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-1á 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, Chi V. Dang and Andre Levchenko, all of the Johns Hopkins University School of Medicine, and Deok-Ho Kim of the University of Washington, Seattle.

The study was funded by the U.S. Public Health Service (contracts N01-HV28180 and HHS-N268201000032c), the National Heart, Lung, and Blood Institute (grant number T32-HL007525), the National Institute of General Medical Sciences (grant number T32-GM008752), the American Heart Association (predoctoral fellowship 10PRE4160120), the Susan G. Komen Foundation (postdoctoral fellowship KG111254), the Foundation for Advanced Research in the Medical Sciences and the Johns Hopkins Institute for Cell Engineering.
Link to the paper: http://stke.sciencemag.org/cgi/content/full/sigtrans;6/262/ra10

Related stories:

Podcast on the Science Signaling paper: http://stke.sciencemag.org/cgi/content/full/sigtrans;6/262/pc5/DC1

Johns Hopkins Researchers Link Cell Division and Oxygen Levels: http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_
researchers_link_cell_division_and_oxygen_levels

Gregg Semenza on how doping in endurance sports and treating cardiovascular disease are interrelated: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/meet_
scientists/gregg_semenza.html

Need Oxygen? Cells Know How to Spend and Save: http://www.hopkinsmedicine.org/news/media/releases/need_oxygen_cells_know
_how_to_spend_and_save

Johns Hopkins Researchers Discover How Breast Cancer Spreads to the Lung: http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_researchers

_discover_how_breast_cancer_spreads_to_lung

Shawna Williams | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Perfect imperfection
03.05.2016 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Quantum Logical Operations Realized with Single Photons

03.05.2016 | Physics and Astronomy

Discovery of a fundamental limit to the evolution of the genetic code

03.05.2016 | Life Sciences

Cavitation aggressive intensity greatly enhanced using pressure at bubble collapse region

03.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>