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.
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.
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.
Sasha Mushegian | EurekAlert!
New study finds distinct microbes living next to corals
22.05.2019 | Woods Hole Oceanographic Institution
Summit charts a course to uncover the origins of genetic diseases
22.05.2019 | DOE/Oak Ridge National Laboratory
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future
When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...
Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells
The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
22.05.2019 | Life Sciences
22.05.2019 | Life Sciences
22.05.2019 | Physics and Astronomy