TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival
TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival
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DOI：
10.1101/gad.1180204
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发表时间：
2004-03-15
影响因子：
10.5
通讯作者：
Lin, WC
中科院分区：
文献类型：
--
作者：
Liu, K;Luo, YH;Lin, WC
TopBP 1（DNA拓扑异构酶II β结合蛋白I）包含多个BRCT结构域，参与复制和DNA损伤检查点。通过其BRCT结构域，TopBP 1与E2 F1相互作用并仅抑制E2 F1，但不抑制其他E2 F因子。E2 F1转录活性的这种调节是由一种不依赖于pRb，但依赖于Brg 1/Brm的机制介导的。TopBP 1招募Brg 1/Brm，SWI/SNF染色质重塑复合物的中心组分，E2 F1响应启动子和抑制E2 F1的活性，但不E2 F2或E2 F3。这种调节在正常细胞生长和DNA损伤过程中对E2 F1依赖性细胞凋亡的控制至关重要。有趣的是，TopBP 1由E2 F诱导，并在G1/S转换期间与E2 F1相互作用。因此，TopBP 1作为一个关键的调节剂，并作为一个负反馈调节E2 F1通过抑制E2 F1依赖性细胞凋亡在G1/S转换以及DNA损伤，以促进细胞存活。
TopBP1 (DNA topoisomerase IIbeta binding protein I> contains multiple BRCT domains and is involved in replication and the DNA damage checkpoint. Through its BRCT domain, TopBP1 interacts with and represses exclusively E2F1 but not other E2F factors. This regulation of E2F1 transcriptional activity is mediated by a pRb-independent, but Brg1/Brm-dependent mechanism. TopBP1 recruits Brg1/Brm, a central component of the SWI/SNF chromatin-remodeling complex, to E2F1-responsive promoters and represses the activities of E2F1, but not E2F2 or E2F3. This regulation is crucial in the control of E2F1-dependent apoptosis during normal cell growth and DNA damage. interestingly, TopBP1 is induced by E2F and interacts with E2F1 during G1/S transition. Thus, TopBP1 functions as a critical modulator and serves as a negative feedback regulator of E2F1 by inhibiting E2F1-dependent apoptosis during G1/S transition as well as DNA damage to promote cell survival.