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In dying cells, immobile CAD (green) is found with the NuMA (red) matrix protein.
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( i3 H/ k) i' }: ^. t9 |% NAn apoptotic cell can cause problems from the grave, including autoimmune disorders, if its DNA is not properly chopped up before death. In human cells, most of this degradation is done by caspase-activated DNase (CAD). On page 851, Lechardeur et al. show that CAD is given free range in the nucleus early in apoptosis, but later gets hitched up—perhaps to prevent it from wreaking havoc outside the cell.8 [4 P O5 M0 J G+ }
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CAD dynamics in living cells indicated that, before apoptosis, CAD and its cobound inhibitor diffused freely in the nucleus. After caspase-3 cleavage of CAD released its inhibitor, CAD continued to move unfettered even as it cleaved DNA. But in time, CAD movements became progressively restricted. Within several hours, after DNA ladders formed, most of the CAD molecules were immobilized. V7 B) x# N! h: t8 {/ P0 W2 |7 D
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By this time, CAD was associated with nonhistone nuclear proteins and colocalized with the NuMA nuclear matrix protein. The delay between CAD activation and immobilization may reflect the time needed for caspase cleavage of other nuclear constituents, possibly matrix proteins, to expose CAD binding sites.
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3 A2 f7 z- ~# bCAD mutants that could not be tied down leaked out of apoptotic cells. Others have shown that a DNase can neutralize antibacterial molecules secreted by neutrophils during inflammation. Tying CAD to the nucleus may be one way to keep it from counteracting those bactericides.(In dying cells, immobile CAD (green) is ) |
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发表于 2009-3-6 08:23
发表于 2015-6-26 09:10
