In the paper “A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications,” appearing this week as an Advanced Online Publication, UMass Medical School Professor Michael R. Green, MD, PhD, and colleagues use a genome-wide RNAi screening tool to identify a dozen genes that affect the function of a crucial protein necessary for glioma cells to grow; further research found a key pathway that appears in laboratory cultures and mouse models to be susceptible to two cancer drugs already in use for other types of cancer.
A hallmark of cancer is uncontrolled cell growth, often caused by overexpression of genes that help cells survive, or underexpression of those genes that induce normal cell death. Genes that are expressed highly in cancer cells and are essential for their survival are appealing targets for drug therapy.
Green’s lab has in recent years developed a clever way of scanning the genome to identify genes that appear to promote the natural process of programmed cell death called “apoptosis”, or that inhibit the growth of cells; Green and colleagues used a technique called genome-wide RNA interference screening—to identify novel genes that regulate the expression of a transcription factor called ATF5 in malignant glioma cells. The discovery of at least one previously unknown genetic pathway that appears to regulate this key transcription factor, and the subsequent determination that the cancer drugs sorafenib and temozolomide inhibit glioma growth point to dramatic new possibilities for potential therapeutics and are exciting advances at the frontier of cancer biology and genetic expression.
ATF5 was first identified as an important pro-survival factor by Dr. Green in 2002.About the University of Massachusetts Medical School
Jim Fessenden | EurekAlert!
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Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
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...
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