Mayo Clinic researchers have found that a protein that initiates a "quality control check" during cell division also directs cell death for those cells damaged during duplication. This knowledge represents a potential "bulls eye" for targeting anti-tumor drugs. The findings appear in the current issue of Science.
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a "quality control inspector." As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells.
"Quality control within dividing cells is essential because mistakes during duplication of the genetic code can lead to cancer," says Donald Tindall, Ph.D., co-leader of the Mayo Clinic Cancer Center prostate cancer research program. "CDK2 is a key protein component in the cellular mechanism that leads to repair of damaged DNA."
If cells pass this quality control checkpoint, they can resume the process of dividing into two daughter cells. If, however, major irreparable discrepancies occur in the genetic code, cells are shunted toward a molecular sequence that leads to death, or apoptosis. Cells have the genetic knowledge to sacrifice themselves for the greater good of the organism rather than to pass on errant genetic codes that can lead to disease. Genetic errors that sneak past the cell's quality control check-points can make the cell prone to develop into cancer.
How It Happens
The Mayo researchers documented that CDK2 infuses high energy into another cellular protein, FOXO1, switching it on as the initial link in a signal that tells the cell to set itself up for apoptosis. CDK2 adds phosphorylation to a specific serine residue on the chain of amino acids that make up FOXO1. In case of robust errors found in the genetic code, CDK2 signals FOXO1 to explicitly call for the cell to produce a set of proteins leading to apoptosis.
"If the cell has minor alterations in the DNA code that can be repaired, those repairs are made," says first author Haojie Huang, Ph.D. "If the genetic message cannot be repaired, our studies show that CDK2 can initiate the steps necessary for cells to order the production of genes involved with cell death, and the errant cell dies without propagating its damaging genetic message to progeny cells of its own."
"As patients and their physicians seek to control or cure tumors, research is providing new approaches to limiting cancer from growing and spreading," Dr. Tindall said. "With this new understanding of the biology driven by critical dual functions of CDK2, the cancer community can focus on ways to regulate a mechanism that the cell contains to prevent damaged genetic messages from being inherited and spread in proliferating tumor cells."
Robert Nellis | EurekAlert!
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Researchers reveal new details on aged brain, Alzheimer's and dementia
21.11.2017 | Allen Institute
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
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,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Materials Sciences
21.11.2017 | Health and Medicine