CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45
CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45
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DOI：
10.1016/s0960-9822(98)79298-x
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发表时间：
1998-04-23
期刊：
影响因子：
9.2
通讯作者：
Wiiliams, LT
中科院分区：
文献类型：
--
作者：
Halenbeck, R;MacDonald, H;Wiiliams, LT
死亡受体如Fas或肿瘤坏死因子（TNF）R1诱导细胞凋亡导致细胞形态的明显变化、半胱天冬酶蛋白酶级联反应的活化以及活化的核酸酶对核染色质的降解。在此，我们描述了从Jurkat细胞中纯化和cDNA克隆一种新的由半胱天冬酶活化的40 kDa核酸内切酶，该蛋白，命名为半胱天冬酶活化核酸酶（CPAN），足以降解裸DNA并诱导幼稚细胞核中的凋亡形态和DNA片段化。CPAN与最近描述的小鼠核酸酶CAD高度同源[1]，并且可能代表人类同源物。我们关于人类cDNA的数据以及关于小鼠同源物的额外数据表明，最近发表的误用序列的30个氨基酸部分[1]是不正确的。我们表明，人CPAN的活性受DFF45 [2]调节，DFF45是活细胞中CPAN表达和稳定在非活性状态所必需的抑制剂。在体外，半胱天冬酶对DFF45的蛋白水解切割导致DFF45片段从CPAN上解离并激活CPAN作为内切核酸酶。CPAN是一种严格调控的核酸内切酶，具有独特的特征，可能代表了一个独特的核酸内切酶家族。
Induction of apoptosis by death receptors such as Fas or tumour necrosis factor (TNF) R1 leads to distinct changes in cell morphology, activation of the caspase protease cascade, and the degradation of nuclear chromatin by activated nucleases, Here, we describe the purification and cDNA cloning of a novel 40 kDa endonuclease from Jurkat cells that is activated by caspases, This protein, designated caspase-activated nuclease (CPAN), is sufficient to degrade naked DNA and to induce apoptotic morphology and DNA fragmentation in naive nuclei. CPAN is highly homologous to a recently described mouse nuclease, CAD [1], and may represent the human homologue, Our data on the human cDNA as well as additional data on the mouse homologue suggest that a 30 amino-acid portion of the recently published misuse sequence [1] is incorrect. We show that the activity of human CPAN is regulated by DFF45 [2], an inhibitor necessary for CPAN expression and stabilization in an inactive state in living cells. Proteolytic cleavage of DFF45 by caspases in vitro leads to dissociation of DFF45 fragments from CPAN and activation of CPAN as an endonuclease. CPAN is a tightly regulated endonuclease with unique characteristics that might represent a distinctive family of endonucleases.