When cells go about the business of dividing, they can get sidelined. Maybe there aren’t enough nutrients. Maybe there aren’t the right signals to resume multiplying. Either way, cells go quiet.
What can restart cell division – the process that drives the development of embryos, the renewal of hair, skin and blood, and the creation of cancer – is a single transcription factor called GABP, according to new research from The Warren Alpert Medical School of Brown University and Rhode Island Hospital.
The work, published online in Nature Cell Biology, introduces a new pathway that can be manipulated to control cell growth. Since cell growth is a fundamental biological process, the research may shed light on everything from miscarriages to muscular dystrophy. The main application, however, is cancer. Since a key characteristic of cancer cells is unchecked growth, the research identifies potential targets for new treatments.
“As a scientist and a physician, I am tremendously excited,” said Alan Rosmarin, M.D., an associate professor in the Department of Medicine and the Department of Molecular Biology, Cell Biology and Biochemistry at Brown and director of clinical oncology research for Lifespan, Rhode Island’s largest health care system. “This discovery not only adds to our basic understanding of cell division, it could lead to better cancer drugs. And they’re needed. Cancer touches everyone.”
During the cell cycle, the four-phase process of cell division, there is a period when the biochemical brakes are put on and cells become inactive. Then the process is kick-started and cells move into the so-called S phase, when DNA is duplicated. This is a critical juncture. If genes are missing or broken, these alterations are passed on to the new cell – and could result in disability or in diseases such as cancer.
So biologists are keenly interested in identifying the accelerators that rev-up cell division. Ets transcription factors, a family of gene-regulating proteins that are major players in embryonic and cancer development, seemed obvious culprits. Rosmarin, a hematologist-oncologist, studies one member of the Ets family called GABP. This transcription factor helps make a variety of cells, including white blood cells. If those cells develop abnormally, leukemia results.
But the exact function of GABP in the cell cycle wasn’t known. Rosmarin wanted to find out. So he and members of his laboratory created mice that carried a mutation – tiny DNA sequences were inserted into their GABP-making gene. These DNA bits would serve as a time bomb of sorts, deleting a critical piece of the gene when given a chemical signal.
From these mice, Rosmarin and his team grew fibroblasts – common connective tissue cells – in a Petri dish with nutrient-rich serum and watched them grow. When they detonated their time bomb, GABP was disrupted, and the fibroblasts’ ability to divide was dramatically reduced. At the same time, other genes known to restart cell division were unchanged.
The team confirmed GABP’s critical role in cell growth another way. Simply forcing dormant cells to make GABP, they found, was enough to rouse cells from their slumber and get them to grow again.
“So we’ve found a new pathway to control cell growth,” Rosmarin said. “Now that we know a way to disrupt GABP and stop division, there is the possibility that a drug can be made to do the same thing in cancer cells.”
Zhong-Fa Yang, an instructor in medicine at Brown and a postdoctoral research fellow at Rhode Island Hospital, was the lead author of the journal article. Stephanie Mott, a Rhode Island Hospital research associate, assisted with the experiments.
The National Heart, Lung and Blood Institute, the National Center for Research Resources and the Herbert W. Saint ’49 Fund at Brown University funded the work.
Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews and maintains an ISDN line for radio interviews. For more information, call the Office of Media Relations at (401) 863-2476.
Wendy Lawton | EurekAlert!
Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Earth Sciences
20.11.2017 | Physics and Astronomy
17.11.2017 | Physics and Astronomy