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 Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>