DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis

DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis
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DOI:
10.1016/s0092-8674(00)80197-x
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发表时间:
1997-04-18
期刊:
影响因子:
64.5
通讯作者:
Wang, XD
Wang, XD
中科院分区:
生物学1区
文献类型:
--
作者:
Liu, XS;Zou, H;Wang, XD

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我们从 HeLa 细胞质中鉴定并纯化了一种蛋白质,该蛋白质被 caspase-3 激活后,会在共孵育细胞核中诱导 DNA 片段化。这种蛋白质被称为 DNA 片段因子 (DFF),是 40 kDa 和 45 kDa 亚基的异二聚体。从其 cDNA 序列确定的 45 kDa 亚基的氨基酸序列表明它是一种新型蛋白质。 Caspase-3 在两个位点切割 45 kDa 亚基,产生活性因子,该因子可产生 DNA 片段化,而无需进一步需要 caspase-3 或其他胞质蛋白。在经历凋亡的细胞中,45 kDa 亚基的切割模式与体外 caspase-3 的切割模式相同。这些数据描绘了细胞凋亡过程中的直接信号转导途径:caspase-3 到 DFF 到 DNA 片段化。
We have identified and purified from HeLa cytosol a protein that induces DNA fragmentation in coincubated nuclei after it is activated by caspase-3. This protein, designated DNA Fragmentation Factor (DFF), is a heterodimer of 40 kDa and 45 kDa subunits. The amino acid sequence of the 45 kDa subunit, determined from its cDNA sequence, reveals it to be a novel protein. Caspase-3 cleaves the 45 kDa subunit at two sites to generate an active factor that produces DNA fragmentation without further requirement for caspase-3 or other cytosolic proteins. In cells undergoing apoptosis, the 45 kDa subunit is cleaved in the same pattern as it is cleaved by caspase-3 in vitro. These data delineate a direct signal transduction pathway during apoptosis: caspase-3 to DFF to DNA fragmentation.