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 Study reveals profound patterns in globally important algae
21.08.2019 | Bigelow Laboratory for Ocean Sciences

nachricht Intestinal bacteria in type 2 diabetes: being overweight is pivotal
21.08.2019 | Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum computers to become portable

Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.

Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...

Im Focus: Towards an 'orrery' for quantum gauge theory

Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics

The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Shape-shifting sheets

21.08.2019 | Materials Sciences

Study reveals profound patterns in globally important algae

21.08.2019 | Life Sciences

New tools to minimize risks in shared, augmented-reality environments

21.08.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>