Featured Research

from universities, journals, and other organizations

Flipping the 'off' switch on cell growth: Protein uses multiple means to help cells cope when oxygen runs low

Date:
February 23, 2013
Source:
Johns Hopkins Medicine
Summary:
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, 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.

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.

Related Articles


"We've long known that this protein, HIF-1α, 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-1α 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-1α 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-1α's own activity is controlled, the team looked for proteins from human cells that would attach to HIF-1α. They found two, MCM3 and MCM7, that limited HIF-1α'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-1α'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-1α 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-1α and the DNA replication complex is reciprocal -- that is, each can shut the other down."


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. E. Hubbi, Kshitiz, D. M. Gilkes, S. Rey, C. C. Wong, W. Luo, D.-H. Kim, C. V. Dang, A. Levchenko, G. L. Semenza. A Nontranscriptional Role for HIF-1 as a Direct Inhibitor of DNA Replication. Science Signaling, 2013; 6 (262): ra10 DOI: 10.1126/scisignal.2003417

Cite This Page:

Johns Hopkins Medicine. "Flipping the 'off' switch on cell growth: Protein uses multiple means to help cells cope when oxygen runs low." ScienceDaily. ScienceDaily, 23 February 2013. <www.sciencedaily.com/releases/2013/02/130223111517.htm>.
Johns Hopkins Medicine. (2013, February 23). Flipping the 'off' switch on cell growth: Protein uses multiple means to help cells cope when oxygen runs low. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/02/130223111517.htm
Johns Hopkins Medicine. "Flipping the 'off' switch on cell growth: Protein uses multiple means to help cells cope when oxygen runs low." ScienceDaily. www.sciencedaily.com/releases/2013/02/130223111517.htm (accessed October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins