Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reading histone modifications, an oncoprotein is modified in return

18.05.2018

Turning genes on and off is an intricate process involving communication between many different types of proteins that interact with DNA.

These communications can go awry, resulting in conditions like cancer. Researchers at the University of Texas MD Anderson Cancer Center have uncovered an unusual form of cross-talk between proteins that affect gene expression, suggesting new ways of inhibiting metastasis in cancer. The findings are published in the Journal of Biological Chemistry.


The light bulb symbolizes TRIM24, a 'histone reader"'protein, which binds chromatin. Chromatin association triggers signaling to TRIM24, marked or 'illuminated' by a post-translational modification called SUMOylation.

Credit: Srikanth Appikonda

Usage Restrictions: Use with attribution only

TRIM24 is an oncoprotein, meaning it is found at a higher abundance in many types of cancer cells than in healthy cells. Michelle Barton's lab at MD Anderson studies what this protein does. Previous research has shown that TRIM24 is, among other things, an epigenetic reader. This means that it detects certain chemical modifications of histones - proteins around which DNA is coiled - and induces other proteins to change their behavior in response, resulting in a different pattern of genes being turned on than if the histone had not been modified.

In the new study, Srikanth Appikonda, a former postdoctoral fellow in Barton's lab, found something unusual. Not only did TRIM24 "read" histone modifications, but the act of reading resulted in TRIM24 itself being modified with a small protein tag called SUMO. In other words, reading the message of the histone made the reader carry its own chemical message.

"This is the first time that we know of that the (histone) itself is imposing a code on the modifiers or readers," Barton said.

What does the addition of SUMO to TRIM24 accomplish? Appikonda, graduate student Kaushik Thakkar and the other team members performed experiments to see how the genes that TRIM24 turned on and off in cancer cells differed when TRIM24 didn't have SUMO attached.

They found that the SUMO-modified TRIM24 seemed to be regulating genes involved in adhesion between cells. This is important because cell adhesion determines whether cancer cells stay in one spot or can travel and metastasize through the body.

"That's really where these cell-adhesion molecules are coming into play, metastasis and migration of cancer cells," Barton said. Multiple proteins are involved in adhesion, and TRIM24 turned some off and some on. Therefore it's not yet clear what net effect TRIM24 has on metastasis in cancer patients. But understanding that TRIM24 is involved in this process gives researchers a place to look to understand how to stop it.

In the meantime, the SUMO modification also can be used as a possible marker in studies of other types of potential new drugs. Cancer researchers are often interested in disrupting TRIM24's interaction with histones, in order to prevent aberrant gene expression. By tracking whether TRIM24 has SUMO attached, researchers can test whether a potential drug has successfully blocked the interaction.

"The exciting thing about learning more about modifications of TRIM24, such as SUMO, is to be able to develop antibodies or other means to detect its presence," Barton said "(This) may be a better predictor of cancers in early stages or could be linked to potential for metastasis."

###

The study was funded by the Cancer Prevention Research Institute of Texas and the National Institutes of Health.

About the Journal of Biological Chemistry

JBC is a weekly peer-reviewed scientific journal that publishes research "motivated by biology, enabled by chemistry" across all areas of biochemistry and molecular biology. The read the latest research in JBC, visit http://www.jbc.org/.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit http://www.asbmb.org.

Sasha Mushegian | EurekAlert!

More articles from Life Sciences:

nachricht The “TRiC” to folding actin
10.08.2018 | Max-Planck-Institut für Biochemie

nachricht SERSitive: New substrates make it possible to routinely detect one molecule in a million
10.08.2018 | Institute of Physical Chemistry of the Polish Academy of Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

Im Focus: A molecular switch may serve as new target point for cancer and diabetes therapies

If certain signaling cascades are misregulated, diseases like cancer, obesity and diabetes may occur. A mechanism recently discovered by scientists at the Leibniz- Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and at the University of Geneva has a crucial influence on such signaling cascades and may be an important key for the future development of therapies against these diseases. The results of the study have just been published in the prestigious scientific journal 'Molecular Cell'.

Cell growth and cell differentiation as well as the release and efficacy of hormones such as insulin depend on the presence of lipids. Lipids are small...

Im Focus: Touring IPP’s fusion devices per virtual-reality viewer

ASDEX Upgrade and Wendelstein 7-X – as if you were there / 360° view of fusion research

You seem to be standing in the plasma vessel looking around: Where otherwise plasmas with temperatures of several million degrees are being investigated, with...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Ph.D. student develops spinning heat shield for future spacecraft

10.08.2018 | Physics and Astronomy

Investigating global air pollution

10.08.2018 | Life Sciences

The “TRiC” to folding actin

10.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>