Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Getting a handle on sensitive cycles

01.04.2003


EMBL researchers discover a mechanism by which cells monitor estrogen



The hormone estrogen is recognized by most people because of its important role in women’s reproductive cycles. It also has other functions in the body: it drives some types of cells to replicate themselves, and it has been linked to the development of tumors. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg have now described a new model of how cells constantly monitor their exposure to estrogen. This work, which appears in the current issue of Molecular Cell, provides new insights into the way estrogen influences the activity of genes. It also suggests new ways to prevent cancer cells from dividing.

Hormones serve as one of the body’s express messenger services; they are frequently used as a signal that tells cells to change their functions or patterns of growth. Estrogen is a small molecule that passes directly into cells; once inside, it latches onto proteins called estrogen receptors that dock onto DNA. As a result, genes are activated and new proteins are produced, changing the cell’s behavior.


The body reacts to both increases and decreases in amounts of estrogen; switching a gene off can be just as important as activating one. Recent experiments have given George Reid, Michael Hübner and Raphaël Métivier in Frank Gannon’s laboratory a new view of how genes can respond to changes in either direction.

Gannon’s team has focused on estrogen receptors since they are the main intermediaries between the estrogen hormone and genes. Their latest work reveals that receptors don’t stay docked onto DNA very long; they regularly get stripped off again and dismantled. New receptors arrive to take their place. This cycle is essential to the way estrogen functions.

"It takes a two-step process for estrogen to switch on a gene," Reid says. "The hormone binds to the receptor and activates it. This complex then docks onto DNA and turns on the gene. If there is no estrogen around, ’unloaded’ receptors still attach themselves to DNA, but the gene won’t be activated. Now suppose that a lot of estrogen arrives, and that gene needs to be activated. The inactive receptor needs to be moved out of the way so that an active one can take its place."

Cells need to be equally sensitive to decreases in the amount of estrogen. This means that genes which have been switched on need to be turned off again. The mechanism is similar: a receptor (in this case, the active form) has to be stripped off the DNA.

"The first thing we discovered was a connection between gene activity, estrogen receptors and the action of intracellular molecular machines called proteasomes, which dismantle proteins," Reid says. "Jan Ellenberg’s group helped us to watch how their behavior changed under different conditions. If proteosomes are active, a receptor can move around quickly, and this puts it into position to contact the genes that respond to it. Without proteasomes, estrogen receptors are immobilized. The cycle is broken: fresh receptors don’t get onto DNA."

Under normal circumstances, however, proteasomes are around to help. The receptors dock onto DNA, and then they need to be stripped off. The Gannon group showed that inactive receptors, after binding to DNA, become loaded with another molecule called ubiquitin, which marks them for destruction by proteasomes.

"With active receptors, the end result is the same, but the sequence of events is a bit different," Reid says. "The active receptor summons other molecules to read the information in the DNA and transcribe it into RNA. After accomplishing this, they, too, become loaded with ubiquitin. Again, this leads to their removal from the gene. What we now understand is that there’s a continuous, active process that strips both types of receptors - free and estrogen-bound – off the DNA, and this is an intrinsic part of how the cell continuously senses estrogen levels."

The constant removal of receptors from genes functions like a sort of security camera that takes a fresh picture of estrogen levels in the cell at regular intervals. It guarantees that the cell can respond to changes when they occur.

"It also shows that this sensing system is dependent on the behavior of other molecular components – ubiquitins, proteasomes and all the cellular systems that control them," Reid says. "That opens up new avenues for therapies in diseases that involve estrogen. We know that the estrogen system is delicate; it’s also important, because it influences how some cells differentiate and divide. These processes go wrong in certain cancers, typically in the breast and the lining of the uterus. Our findings suggest that you might be able to stop the proliferative effects of estrogen by interfering with these other processes."

Russ Hodge | EurekAlert!
Further information:
http://www.embl-heidelberg.de/

More articles from Life Sciences:

nachricht New technique unveils 'matrix' inside tissues and tumors
29.06.2017 | University of Copenhagen The Faculty of Health and Medical Sciences

nachricht Designed proteins to treat muscular dystrophy
29.06.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making Waves

Computer scientists use wave packet theory to develop realistic, detailed water wave simulations in real time. Their results will be presented at this year’s SIGGRAPH conference.

Think about the last time you were at a lake, river, or the ocean. Remember the ripples of the water, the waves crashing against the rocks, the wake following...

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Nanostructures taste the rainbow

29.06.2017 | Physics and Astronomy

New technique unveils 'matrix' inside tissues and tumors

29.06.2017 | Life Sciences

Cystic fibrosis alters the structure of mucus in airways

29.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>