The insight emerged from a long-running study of a protein called PMR1, the key player in an unusual mechanism that cells use to quickly stop production of certain important proteins.
Researchers discovered that PMR1 is activated – or “turned on – by another molecule, an energy-packing protein called Src (pronounced “sark”).Discovered in 1977, Src became the first “oncogene” – mutated genes that help make cells cancerous. Oncogenes are altered forms of genes that control cell growth and cell division.
The study by researchers with the Ohio State University Comprehensive Cancer Center is published in the March 9 issue of the journal Molecular Cell.
“The link between Src and cancer was discovered 30 years ago, but to this day, we still don't know its exact role in tumor development,” says principal investigator Daniel R. Schoenberg, professor of molecular and cellular biochemistry.
“Our data suggest that Src may promote cancer by causing PMR1 to halt production of proteins that normally put the brakes on cell growth – tumor-suppressor proteins, for example, or other growth-regulating proteins.”
In healthy cells, Src helps control cell proliferation, differentiation, survival and movement. Mutated Src is found in about half of all colon, liver, lung, breast and pancreatic tumors, and the amount of Src can be significantly higher in cancer cells compared to normal cells.
Earlier research led by Schoenberg found that PMR1 helps control protein production by destroying particular messenger RNAs (mRNAs), molecules that carry the information used to assemble a protein.
That work showed that PMR1 attaches to the mRNAs and remains there as a silent passenger. If it receives the proper signal, however, the protein chops up and destroys the mRNA, which instantly stops production of that protein.
Cells use that mechanism to control the production of proteins such as growth factors, which activate genes in response to a hormone or other signal.
PMR1 also plays a key role in Cooley's anemia, which causes the loss of red blood cells in infants and children.
For the present study, Schoenberg and coauthor Yong Peng, a research associate in Schoenberg's laboratory, wanted to learn how PMR1 is activated to attach to mRNAs.
They found that activation occurs when PMR1 is momentarily joined by an unidentified enzyme. Contact with this enzyme changes the properties of PMR1, and this enables it to join with, or bind to, its target mRNA.
Peng then used monoclonal antibodies to isolate PMR1 and the enzyme while the two were bound together, capturing both. After separating the two, the investigators identified the enzyme as Src, which is a member of a large family of molecules called tyrosine kinases. These molecules act like switches that turn other molecules on and off, including PMR1.
“That's the real excitement about this paper,” Schoenberg says. “We came at this with an interest in mRNA decay, and we may have stumbled across a fundamental mechanism of cancer.”
Next, Schoenberg and his associates Xiaoqiang Liu and Elizabeth Murray will use three cancer-cell lines to try to identify what messenger RNAs – which will also tell them what proteins – are targeted and destroyed by PMR1.
“That will help tell us whether Src works through PMR1 to contribute to cancer,” Schoenberg says.
Funding from the National Institute for General Medical Sciences supported this research.
Darrell E. Ward | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy