The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis

The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis
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DOI:
10.1073/pnas.95.15.8461
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发表时间:
1998-07-21
影响因子:
11.1
通讯作者:
Wang, XD
Wang, XD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu, XS;Li, P;Wang, XD

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我们在这里报告的重组DNA片段化因子(DFF),40和45 kDa的异源二聚体蛋白质,导致细胞核中的凋亡变化的途径的重建。需要DFF 40和DFF 45的共表达来产生重组DFF,当DFF 45被半胱天冬酶-3切割时,重组DFF被激活。DFF 45的裂解片段与DFF 40(DFF的活性组分)解离。纯化的DFF IO表现出固有的DNA酶活性,显着刺激染色质相关蛋白组蛋白H1和高迁移率族蛋白。当与细胞核一起孵育时,DFF IO也触发染色质凝聚。这些数据表明,DFF IO足以在细胞凋亡期间触发DNA片段化和染色质凝聚。
We report here the reconstitution of a pathway that leads to the apoptotic changes in nuclei by using recombinant DNA fragmentation factor (DFF), a heterodimeric protein of 40 and 45 kDa. Coexpression of DFF40 and DFF45 is required to generate recombinant DFF, which becomes activated when DFF45 is cleaved by caspase-3. The cleaved fragments of DFF45 dissociate from the DFF40, the active component of DFF. Purified DFF IO exhibited an intrinsic DNase activity that was markedly stimulated by chromatin-associated proteins histone H1 and high mobility group proteins. DFF IO also triggered chromatin condensation when incubated with nuclei. These data suggest that DFF IO is sufficient to trigger both DNA fragmentation and chromatin condensation during apoptosis.