This brake is a protein that appears to stop the cascade of molecular events that leads to the activation of a cancer-producing gene, or oncogene, that causes the tumors. The oncogene, called Ras, was one of the first oncogenes ever discovered and has been implicated in more than half of all human cancers.
The new finding could have important medical implications, the researchers said, since the gene involved and the processes that regulate its activation are the same in humans as in yeasts. Similar genes in different species are known as homologs.
The researchers reported their findings in the June 23, 2006, issue of the journal Molecular Cell. The study was supported by the National Institutes of Health, the Children's Tumor Foundation, and the Department of Defense's Neurofibromatosis Foundation.
Neurofibromatosis 1 occurs in about one in 3,500 newborn children and is characterized by multiple growths, or neurofibromas, on or under the skin, usually along nerve fibers. Occasionally, the neurofibromas become large and disfiguring, or develop on the brain or spinal cord. About half of patients with neurofibromatosis 1 have learning disabilities.
The Duke researchers focused their attention on the neurofibromatosis 1 gene, which contains the blueprint for the production of neurofibromin, a protein found primarily in nerve cells. A tumor-suppressor protein, neurofibromin keeps the Ras gene in check and prevents abnormal cell growth.
"We know that patients with neurofibromatosis 1 have defects, or mutations, in the neurofibromin gene," said lead researcher Joseph Heitman, M.D., Ph.D. "As a consequence, the protein it produces becomes unstable and can no longer effectively suppress the Ras oncogene. As a result, Ras becomes over-stimulated, and this in turn leads to the formation of the tumors along the nerve fivers."
Scientists have not fully understood how and why the mutated neurofibromin gene leads to activation of the Ras oncogene. In the current study, the researchers discovered two novel proteins that appear to be necessary in neurofibromin's ability to regulate Ras. The team named these novel proteins Gpb1 and Gbp2.
"When the two proteins are present, they keep the yeast neurofibromin homologs stabilized, effectively blocking the molecular signaling pathway that activates Ras," said Toshiaki Harashima, Ph.D., first author of the study. Harashima, a cell biologist, worked as a senior postdoctoral fellow in Heitman's laboratory and now is at the National Institute for Basic Biology in Japan.
"Our findings add to basic understanding of how neurofibromin is stabilized," Harashima said. "By shedding light on these fundamental processes, we hope we can help in the development of new drugs or therapies to block the activation of Ras and prevent this disease."
According to Heitman, yeast, a member of the fungus family, can serve as an effective model for studying basic molecular processes in humans, beyond those involved in neurofibromatosis 1, because the signaling pathways of many genes are remarkably similar in both types of organisms.
"These processes have remained in the genomes of yeasts and humans over a billion years of evolution," Heitman said. "Now that scientists have mapped the entire genome of the baker's yeast we study, Saccharomyces cerevisiae, we are able to look for human gene equivalents using all the latest experimental methods that have been developed over the years using yeasts."
Richard Merritt | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy