The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
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DOI：
10.1371/journal.pone.0044817
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hidaka M
中科院分区：
文献类型：
--
作者：
Fujikane R;Sanada M;Sekiguchi M;Hidaka M
O 6-甲基鸟嘌呤是一种烷基化的DNA碱基，具有很强的致突变性。含有这种病变的细胞通过诱导细胞凋亡而消除，这与错配修复（MMR）蛋白的功能有关。逆转录病毒介导的基因陷阱诱变用于分离与诱导凋亡相关的新基因，所述诱导凋亡由用烷化剂N-甲基-N-亚硝基脲（MNU）处理触发。这份报告描述了一个新的基因，MAPO 2（O 6-甲基鸟嘌呤诱导的细胞凋亡2），这是最初注释为C1 orf 201的鉴定。MAPO 2基因在多种多细胞生物中是保守的，并编码含有特征性PxPxxY重复序列的蛋白质。为了阐明该基因产物在细胞凋亡途径中的功能，构建了来源于HeLa MR细胞的人细胞系，其中MAPO 2基因通过表达特异性miRNA而被稳定敲除。敲除的细胞以与HeLa MR相同的速率生长，因此表明MAPO 2在细胞生长中不起作用。MNU处理后，HeLa MR细胞和敲除细胞均发生G2/M期细胞周期阻滞，而敲除细胞中亚G1期细胞群的产生明显低于HeLa MR细胞。此外，巴克和caspase-3的激活，以及线粒体膜的去极化，诱导凋亡的标志，也被抑制在敲低细胞。这些结果表明，MAPO 2基因产物可能积极促进O 6-甲基鸟嘌呤引发的细胞凋亡的诱导。
O6-Methylguanine, one of alkylated DNA bases, is especially mutagenic. Cells containing this lesion are eliminated by induction of apoptosis, associated with the function of mismatch repair (MMR) proteins. A retrovirus-mediated gene-trap mutagenesis was used to isolate new genes related to the induction of apoptosis, triggered by the treatment with an alkylating agent, N-methyl-N-nitrosourea (MNU). This report describes the identification of a novel gene, MAPO2 (O6-methylguanine-induced apoptosis 2), which is originally annotated as C1orf201. The MAPO2 gene is conserved among a wide variety of multicellular organisms and encodes a protein containing characteristic PxPxxY repeats. To elucidate the function of the gene product in the apoptosis pathway, a human cell line derived from HeLa MR cells, in which the MAPO2 gene was stably knocked down by expressing specific miRNA, was constructed. The knockdown cells grew at the same rate as HeLa MR, thus indicating that MAPO2 played no role in the cellular growth. After exposure to MNU, HeLa MR cells and the knockdown cells underwent cell cycle arrest at G2/M phase, however, the production of the sub-G1 population in the knockdown cells was significantly suppressed in comparison to that in HeLa MR cells. Moreover, the activation of BAK and caspase-3, and depolarization of mitochondrial membrane, hallmarks for the induction of apoptosis, were also suppressed in the knockdown cells. These results suggest that the MAPO2 gene product might positively contribute to the induction of apoptosis triggered by O6-methylguanine.
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影响因子：
2.7
作者：
Glassner, BJ;Weeda, G;Samson, LD
通讯作者：
Samson, LD
DOI：
10.1016/0921-8777(94)90071-x
发表时间：
1994-05-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
ITO, T;NAKAMURA, T;SEKIGUCHI, M
通讯作者：
SEKIGUCHI, M
影响因子：
16
作者：
Yoshioka, Ken-Ichi;Yoshioka, Yoshiko;Hsieh, Peggy
通讯作者：
Hsieh, Peggy
DOI：
10.1073/pnas.96.19.10764
发表时间：
1999-09-14
影响因子：
11.1
作者：
Hickman, MJ;Samson, LD
通讯作者：
Samson, LD
影响因子：
3.8
作者：
Takagi, Y;Takahashi, M;Sekiguchi, M
通讯作者：
Sekiguchi, M