How an enzyme tells stem cells which way to divideMay 14, 2009Driving Miranda, a protein in fruit flies crucial to switch a stem cell's fate, is not as complex as biologists thought, according to University of Oregon biochemists. They've found that one enzyme (aPKC) stands alone and acts as a traffic cop that directs which roads daughter cells will take. "Wherever aPKC is at on a cell's cortex or membrane, Miranda isn't," says Kenneth E. Prehoda, a professor in the chemistry department and member of the UO's Institute of Molecular Biology. When a stem cell duplicates into daughter cells, the side, or cortical domain, containing aPKC (atypical protein kinase C) continues as a stem cell, while the other domain with Miranda becomes a differentiated cell such as a neuron that forms the central nervous system. Prehoda and co-author Scott X. Atwood, who studied in Prehoda's lab and recently earned his doctorate, describe how the mechanism works in the May 12 issue of the journal Current Biology. Instead of a complex cascade of protein deactivation steps that many biologists have theorized, Prehoda said, aPKC strips phosphate off an energy-transfer nucleotide known as ATP and then attaches it to Miranda. This process forces Miranda away from aPKC and helps determine the fates of subsequent daughter cells. "This process is pretty simple," he said, when viewed from a biochemical perspective. "What happens is that Miranda gets phosphorylated by aPKC, turning it into an inactivated substrate and pushing it into another location in the cell." Much of the paper in Current Biology is devoted to why the more complex scenarios are not accurate. "There have been a lot of ideas on how this works, and most seemed to be really complicated and difficult to explain. We have found it's a much simpler mechanism," Prehoda said, adding that the mechanism likely is similar in many other types of cells, not just stem cells. "It's a basic-research question. How does this polarity occur? In order to develop stem cell-specific therapeutics based on a rational methodology you have to understand the mechanism," he said. If Miranda is improperly isolated into other regions by aPKC, the stem cell divides symmetrically, with both daughter cells adopting the same fate, In turn, Prehoda said, these cells can become tumorous as they continue to rapidly divide without proper polarization. University of Oregon |
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| Related Stem Cell Current Events and Stem Cell News Articles First reconstitution of an epidermis from human embryonic stem cells Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells. Your Own Stem Cells Can Treat Heart Disease The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells. U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning. Researchers find potential treatment for Huntington's disease Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease. Researchers 'notch' a victory toward new kind of cancer drug Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed. UCI embryonic stem cell therapy restores walking ability in rats with neck injuries The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage. First use of antibody and stem cell transplantation to successfully treat advanced leukemia For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options. Immune therapy can protect against or treat later lymphoma Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection. Immunotherapy demonstrates long-term success in treating lymphoma Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT). Of mice and men: Stem cells and ethical uncertainties The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics. More Stem Cell Current Events and Stem Cell News Articles |
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