The findings published in Nature Genetics have implications for pharmacogenetics, the study of how inherited variations may affect drug metabolism and response, and present a target for future ‘designer’ cancer therapies.
The p53 tumor-suppressor protein removes damaged cells by a programmed cell death (apoptosis). When the p53 gene is mutated - as it is in approximately half of all human cancers - damaged cells do not die, but rather continue to grow and divide and eventually form a tumor. The two most common polymorphic forms of p53 are p53Pro72 and p53Arg72 and the distribution varies in different ethnic groups. The two forms differ by just one amino acid in the protein sequence. Several years ago, the LICR team discovered that the ability of p53 to control apoptosis is regulated by the ASPP family of proteins.
In this study, the investigators showed that the ASPP family preferentially regulates the p53Pro72 over p53Arg72 form. These results suggest that ASPP protein levels determine cancer susceptibility in people with the p53Pro72 form, the prevalence of which is linked closely to latitude.
According to Professor Xin Lu, the senior author of the study and Director of the LICR Branch, the occurrence of the p53Pro72 form is highest in ethnic populations from around the equator. “It’s really interesting to speculate whether the increased exposure to DNA-damaging ultraviolet radiation has resulted in the need for a second level of p53-regulation. The results are important for furthering our understanding of how p53, the tumor suppressor, is regulated, and also offers intriguing hints about how these regulatory mechanisms might have evolved.”
While speculations about how the mechanism evolved are largely academic at this stage, Professor Lu says the findings have practical applications for future cancer therapies and the growing field of pharmacogenetics. “It’s not hard to imagine a scenario in the future where we might examine the p53 sequence of a cancer patient as part of tailoring an individualized therapeutic strategy. If the patient has p53Pro72, then she might get a specific therapy that alters ASPP protein levels to re-activate p53’s anti-cancer function. If the patient has p53Arg72, we know the therapy would be less effective.”
Sarah White | alfa
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21.09.2017 | Christian-Albrechts-Universität zu Kiel
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21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
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