Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.
Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.
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DOI：
10.4161/cc.27983
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kadomatsu K
中科院分区：
文献类型：
--
作者：
Murakami-Tonami Y;Kishida S;Takeuchi I;Katou Y;Maris JM;Ichikawa H;Kondo Y;Sekido Y;Shirahige K;Murakami H;Kadomatsu K
在有丝分裂过程中，染色体凝聚需要凝聚蛋白复合体；然而，该复合体在间期的作用尚不清楚。神经母细胞瘤是儿童最常见的颅外实体瘤，通常是致命的。在人神经母细胞瘤中，MYCN基因扩增与预后不良相关。本研究表明，编码凝缩蛋白复合物亚基SMC2的基因受MYCN的转录调控。SMC2还与MYCN合作转录调控DNA损伤应答基因。SMC2下调诱导DNA损伤，并在mycn扩增/过表达细胞中显示协同致死反应，导致人神经母细胞瘤细胞凋亡。最后，本研究发现，当SMC2表达较低时，mycn扩增肿瘤患者的生存率提高。这些结果确定了SMC2在DNA损伤反应中的新功能，我们提出SMC2（或凝缩蛋白复合体）是治疗mycn扩增的神经母细胞瘤的新分子靶点。
The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis. This study demonstrates that the gene encoding the condensin complex subunit SMC2 is transcriptionally regulated by MYCN. SMC2 also transcriptionally regulates DNA damage response genes in cooperation with MYCN. Downregulation of SMC2 induced DNA damage and showed a synergistic lethal response in MYCN-amplified/overexpression cells, leading to apoptosis in human neuroblastoma cells. Finally, this study found that patients bearing MYCN-amplified tumors showed improved survival when SMC2 expression was low. These results identify novel functions of SMC2 in DNA damage response, and we propose that SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma.
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影响因子：
10.5
作者：
D'Ambrosio, Claudio;Schmidt, Christine Katrin;Uhlmann, Frank
通讯作者：
Uhlmann, Frank
DOI：
10.1083/jcb.200908026
发表时间：
2010-02-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fazzio TG;Panning B
通讯作者：
Panning B
影响因子：
10.5
作者：
Fernandez, PC;Frank, SR;Amati, B
通讯作者：
Amati, B
DOI：
10.1073/pnas.1012351108
发表时间：
2011-02-22
影响因子：
11.1
作者：
Cole, Kristina A.;Huggins, Jonathan;Maris, John M.
通讯作者：
Maris, John M.
影响因子：
4.8
作者：
Beierle, Elizabeth A.;Trujillo, Angelica;Golubovskaya, Vita M.
通讯作者：
Golubovskaya, Vita M.