Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments
Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments
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DOI：
10.1016/j.yexcr.2004.03.050
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发表时间：
2004-07-15
影响因子：
3.7
通讯作者：
Jacobson, MK
中科院分区：
文献类型：
--
作者：
Meyer-Ficca, ML;Meyer, RG;Jacobson, MK
聚（adp -核糖）糖水解酶（PARG）是已知唯一能催化adp -核糖（ADPR）聚合物水解释放adp -核糖的蛋白质。虽然有许多基因编码不同的聚（adp -核糖）聚合酶（parp），它们都合成adp -核糖聚合物，但在哺乳动物细胞中只检测到一个编码PARG的基因。在这里，我们描述了人类PARG mRNA的两个剪接变体，除了全长PARG蛋白（hPARG111）外，还导致PARG亚型102 kDa （hPARG102）和99 IcDa （hPARG99）的表达。这些剪接变体与hPARG111的不同之处在于缺乏外显子1 （hparg102）或外显子1和2 （hPARG99）。它们是通过利用PARG基因5'非翻译区的模糊剪接供体位点产生的。hPARG111亚型定位于细胞核，而hparg102和hPARG99是细胞质蛋白。hPARG111的核靶向是由于外显子1中的核定位信号（NLS）定位于氨基酸（aa） (CTKRPRW16)-C-10。免疫细胞化学、免疫印迹和PARG酶活性测量表明，在没有和存在基因毒性应激的情况下，细胞中PARG的细胞质同工型占了大部分PARG活性。细胞parp的主要细胞质定位是有趣的，因为大多数已知的细胞parp都有一个核定位。(C) 2004爱思唯尔公司版权所有。
Poly(ADP-ribose) glycohydrolase (PARG) is the only protein known to catalyze hydrolysis of ADP-ribose (ADPR) polymers to free ADP-ribose. While numerous genes encode different poly(ADP-ribose) polymerases (PARPs) that all synthesize ADP-ribose polymer, only a single gene coding, for PARG has been detected in mammalian cells. Here, we describe two splice variants of human PARG mRNA, which lead to expression of PARG isoforms of 102 kDa (hPARG102) and 99 IcDa (hPARG99) in addition to the full-length PARG protein (hPARG111). These splice variants differ from hPARG111 by the lack of exon 1 (hPARG 102) or exons 1 and 2 (hPARG99). They are generated by the utilization of ambiguous splice donor sites in the PARG gene 5' untranslated region. The hPARG111 isoform localizes to the nucleus, whereas hPARG 102 and hPARG99 are cytoplasmic proteins. The nuclear targeting of hPARG111 is due to a nuclear localization 16 signal (NLS) in exon 1 that was mapped to the amino acids (aa) (CTKRPRW16)-C-10. Immunocytochemistry, immunoblotting, and PARG enzyme activity measurements show that the cytoplasmic isoforms of PARG account for most of the PARG activity in cells in the absence and presence of genotoxic stress. The predominantly cytoplasmic location of cellular PARG is intriguing as most known cellular PARPs have a nuclear localization. (C) 2004 Elsevier Inc. All rights reserved.