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 Charge Order and Electron Localization in a Molecule-Based Solid
22.01.2018 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

The world's most powerful acoustic tractor beam could pave the way for levitating humans

22.01.2018 | Power and Electrical Engineering

Siberian scientists learned how to reduce harmful emissions from HPPs

22.01.2018 | Power and Electrical Engineering

Combination of Resistance Genes Offers Better Protection for Wheat against Powdery Mildew

22.01.2018 | Agricultural and Forestry Science

VideoLinks
B2B-VideoLinks
More VideoLinks >>>