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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>