The apoptotic effects of toosendanin are partially mediated by activation of deoxycytidine kinase in HL-60 cells.
The apoptotic effects of toosendanin are partially mediated by activation of deoxycytidine kinase in HL-60 cells.
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川楝素的凋亡作用部分是由 HL-60 细胞中脱氧胞苷激酶的激活介导的
DOI：
10.1371/journal.pone.0052536
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Ju J;Qi Z;Cai X;Cao P;Huang Y;Wang S;Liu N;Chen Y
三萜仙丹素（TSN）通过诱导多种癌细胞的凋亡而显示出强大的细胞毒活性。然而，TSN对细胞凋亡的作用靶点和机制尚不清楚。本研究通过序列亲和层析法捕获了HL-60细胞中TSN的特异性结合蛋白，进一步鉴定为脱氧胞苷激酶（dCK）。通过直接激活dCK和dCK抑制剂抑制TSN诱导的细胞凋亡，证实了dCK是TSN在HL-60细胞中部分参与凋亡的靶点。此外，TSN激活dCK是构象改变的结果，而不是自磷酸化。我们的研究结果进一步表明，除了dCK激活肿瘤细胞的dATP增加外，dCK还可能参与了细胞凋亡的调控。
Triterpenoid toosendanin (TSN) exhibits potent cytotoxic activity through inducing apoptosis in a variety of cancer cell lines. However, the target and mechanism of the apoptotic effects by TSN remain unknown. In this study, we captured a specific binding protein of TSN in HL-60 cells by serial affinity chromatography and further identified it as deoxycytidine kinase (dCK). Combination of direct activation of dCK and inhibition of TSN-induced apoptosis by a dCK inhibitor confirmed that dCK is a target for TSN partially responsible for the apoptosis in HL-60 cells. Moreover, the activation of dCK by TSN was a result of conformational change, rather than auto-phosphorylation. Our results further imply that, in addition to the dATP increase by dCK activation in tumor cells, dCK may also involve in the apoptotic regulation.
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影响因子：
3.9
作者：
Keszler, G;Virga, S;Staub, M
通讯作者：
Staub, M
影响因子：
3.5
作者：
McSorley, Theresa;Ort, Stephan;Konrad, Manfred
通讯作者：
Konrad, Manfred
影响因子：
--
作者：
Sato, Shin-ichi;Murata, Asako;Uesugi, Motonari
通讯作者：
Uesugi, Motonari
影响因子：
1.3
作者：
Keszler, G;Spasokoukotskaja, T;Sasvari-Szekely, M
通讯作者：
Sasvari-Szekely, M
影响因子：
2.7
作者：
Raynal, Noel J. -M.;Momparler, Louise F.;Momparler, Richard L.
通讯作者：
Momparler, Richard L.