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Donald Nicholson (Merck Frosst Center for Therapeutic Research, Pointe-Claire-Dorval, Quebec, Canada) and colleagues have identified a protein called Hippi as one possible mediator of Huntington disease (HD) neuronal cell death.
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HD begins with expansion of the polyglutamine repeats in the huntingtin protein (Htt). This frees up Hip1 protein, which normally binds to Htt. Free Hip1 can then bind to the Hippi protein identified by Nicholson, and the two proteins join in a complex with procaspase 8, although this interaction appears to be indirect. Once two or more molecules of procaspase 8 are in close proximity, they should be able to cleave and activate each other, thus initiating a program of apoptosis.The discovery of Hippi is exciting, but characterization of cells and mice lacking Hippi may be even more so. Crossing these mice to Htt mutant mice will allow a determination of whether the Hip1/Hippi pathway mediates the major effects of HD. The phenotype of the Hippi mutants themselves may give a clue about what this regulated apoptosis pathway does in normal individuals.
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: o; E, W( f: w; Q @5 ~Gervais, F.G., et al. 2002. Nat. Cell Biol. 10.1038/ncb735(Hippi (green) might help kill this corti) |
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发表于 2009-3-6 00:09
发表于 2015-6-10 09:18
