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Apoptosis induced DNA fragmentation

Reactome ID: R-HSA-140342

中文名称

凋亡诱导的DNA片段化

通路描述

对凋亡信号的响应中,DNA片段化的实现部分通过凋亡核酸酶的活性完成,称为DNA片段化因子(DFF)或 caspase 激活的 DNA 酶(CAD)(综述 Widlak 和 Garrard, 2005)。在非凋亡细胞中,DFF 是由 45 kD 的伴侣和抑制亚基(DFF45)/CAD 抑制剂(ICAD-L)组成的核异二聚体,以及 40 kD 的核酸酶亚基(DFF40/CAD)(Liu 等 1997, 1998; Enari 等 1998)。在凋亡期间,活化的 caspase-3 或 -7 切割 DFF45/ICAD 释放活性 DFF40/CAD 核酸酶。DFF 的活性在多个阶段受到严格调控。在翻译期间,DFF45/ICAD、Hsp70 和 Hsp40 蛋白质在翻译期间确保 DFF40 的正确折叠发挥作用(Sakahira 和 Nagata, 2002)。DFF40 的核酸酶活性由组蛋白 H1、拓扑异构酶 II 和 HMGB1/2 等染色体蛋白增强(Widlak 等,2000)。此外,抑制剂(DFF45/35; ICAD-S/L)以化学计量过剩产生(Widlak 等,2003)。
英文描述
Apoptosis induced DNA fragmentation DNA fragmentation in response to apoptotic signals is achieved, in part, through the activity of apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) (reviewed in Widlak and Garrard, 2005). In non-apoptotic cells, DFF is a nuclear heterodimer consisting of a 45 kD chaperone and inhibitor subunit (DFF45)/inhibitor of CAD (ICAD-L)] and a 40 kD nuclease subunit (DFF40/CAD)( Liu et al. 1997, 1998; Enari et al. 1998). During apoptosis, activated caspase-3 or -7 cleave DFF45/ICAD releasing active DFF40/CAD nuclease. The activity of DFF is tightly controlled at multiple stages. During translation, DFF45/ICAD, Hsp70, and Hsp40 proteins play a role in insuring the appropriate folding of DFF40 during translation(Sakahira and Nagata, 2002). The nuclease activity of DFF40 is enhanced by the chromosomal proteins histone H1, Topoisomerase II and HMGB1/2(Widlak et al., 2000). In addition, the inhibitors (DFF45/35; ICAD-S/L) are produced in stoichiometric excess (Widlak et al., 2003).

所含基因

13 个基因