PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration.
PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration.
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DOI：
10.1186/1478-811x-8-31
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发表时间：
2010-12-22
期刊：
影响因子：
--
通讯作者：
Babu PP
中科院分区：
文献类型：
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作者：
Chaitanya GV;Steven AJ;Babu PP
聚（ADP-核糖）聚合酶-1（PARP-1）的正常功能是响应于各种细胞应激通过添加聚（ADP核糖）聚合物来常规修复DNA损伤。最近，已经广泛认识到PARP-1还参与从细胞存活到几种形式的细胞死亡的多种生理和病理功能，并且已经涉及基因转录、免疫应答、炎症、学习、记忆、突触功能、血管生成和衰老。在CNS中，PARP抑制减弱病理学如脑缺血、创伤和兴奋性毒性中的损伤，证明PARP-1在这些病理学中的中心作用。PARP-1也是几种“自杀性”蛋白酶的优选底物，自杀性蛋白酶（半胱天冬酶、钙蛋白酶、组织蛋白酶、颗粒酶和基质金属蛋白酶（MMP））对PARP-1的蛋白水解作用产生几种具有不同分子量的特异性蛋白水解切割片段。这些PARP-1特征片段是独特细胞死亡程序中蛋白酶活性特定模式的公认生物标志物。本文综述了对PARP-1的特异性自杀性蛋白酶活性，以产生可以识别病理生理学中涉及的关键蛋白酶和特定形式的细胞死亡的签名PARP-1片段。一些PARP-1片段及其相关的结合伴侣在控制不同形式的细胞死亡中所起的作用也进行了讨论。
The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine repair of DNA damage by adding poly (ADP ribose) polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs)) on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.