Tumors with nonfunctional retinoblastoma protein are killed by reduced γ-tubulin levels.
Tumors with nonfunctional retinoblastoma protein are killed by reduced γ-tubulin levels.
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DOI：
10.1074/jbc.m112.357038
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发表时间：
2012-05-18
期刊：
影响因子：
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通讯作者：
Alvarado-Kristensson M
中科院分区：
文献类型：
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作者：
Ehlén Å;Rosselló CA;von Stedingk K;Höög G;Nilsson E;Pettersson HM;Jirström K;Alvarado-Kristensson M
背景：γ-微管蛋白通过直接结合DNA调节E2 F调节的启动子的表达。结果：RB 1和γ-微管蛋白通过与各自的基因启动子结合调节彼此的表达。结论：在无功能RB 1的肿瘤中，γ-微管蛋白水平的降低导致细胞凋亡的诱导。意义：RB 1/γ-tubulin信号网络可作为肿瘤治疗的新靶点。在各种肿瘤中，生长控制的失活是通过干扰RB 1信号通路来实现的。在这里，我们描述了RB 1和γ-微管蛋白通过结合各自的基因启动子来调节彼此的表达。RB 1和γ-微管蛋白水平的同时降低导致凋亡基因如caspase 3的E2 F1依赖性上调。我们报告说，在各种肿瘤类型中，γ-微管蛋白和RB 1的表达水平之间存在负相关性，并且在具有无功能RB 1的肿瘤细胞系中，γ-微管蛋白蛋白水平的降低导致细胞凋亡的诱导。因此，RB 1/γ-微管蛋白信号网络可以被认为是癌症治疗的新靶点。
Background: γ-Tubulin moderates the expression of E2F-regulated promoters by direct binding to DNA. Results: RB1 and γ-tubulin proteins moderate each other's expression by binding to their respective gene promoters. Conclusion: Reduction of γ-tubulin protein levels in tumors with nonfunctional RB1 leads to induction of apoptosis. Significance: The RB1/γ-tubulin signal network can be considered as a new target for cancer treatment. In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ-tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ-tubulin protein levels results in an E2F1-dependent up-regulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ-tubulin and RB1 and that in tumor cell lines with a nonfunctioning RB1, reduction of γ-tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ-tubulin signal network can be considered as a new target for cancer treatment.