Drosophila Caliban mediates G1-S transition and ionizing radiation induced S phase checkpoint
Drosophila Caliban mediates G1-S transition and ionizing radiation induced S phase checkpoint
复制标题
果蝇 Caliban 介导 G1-S 转变和电离辐射诱导的 S 期检查点
DOI：
10.1080/15384101.2018.1524237
复制
发表时间：
2018-09
期刊：
影响因子：
4.3
通讯作者：
Xiaolin Bi
中科院分区：
文献类型：
--
作者：
Fanghua Song;Dong Li;Yajie Wang;Xiaolin Bi
摘要细胞周期进程受多种内在和外在细胞因子的精确调控。了解细胞周期调控的潜在机制对于解决如何实现正常发育和组织稳态至关重要。在这里，我们提出了一种新的细胞周期调节剂Caliban（Clbn），果蝇直系同源的人血清学定义的结肠癌抗原1（SDCCAG 1）基因。我们发现，电离辐射诱导表达的clbn，和clbn的过表达的G1-到-S细胞周期的转换在果蝇中的块，而苍蝇损失的clbn有缺陷的S期检查点在响应于辐射。从机制上讲，诱导表达的clbn抑制E2 F1活性和下调DNA复制和表达的下游目标细胞周期蛋白E，一个关键的调节G1到S的转变。同时，clbn过表达导致CDK抑制剂Dacapo（Dap）的上调，并且当e2 f1过表达时，上调的Dap降低。此外，clbn的表达在具有e2 f1过表达或rbf 1敲低的细胞中下调，表明Clbn和E2 F1在介导G1至S转变中起拮抗作用。因此，我们提供的遗传证据表明，Clbn与E2 F1在调节细胞周期的进展，和Clbn是所需的S期细胞周期检查点响应DNA损伤。
ABSTRACT Cell cycle progression is precisely regulated by diverse extrinsic and intrinsic cellular factors. Understanding the underlying mechanisms of cell cycle regulation is essential to address how normal development and tissue homeostasis are achieved. Here, we present a novel cell cycle regulator Caliban (Clbn), the Drosophila ortholog of human Serologically defined colon cancer antigen 1 (SDCCAG1) gene. We show that ionizing radiation induces expression of clbn, and over-expression of clbn blocks G1-to-S cell cycle transition in Drosophila, while flies loss of clbn have defective S phase checkpoint in response to irradiation. Mechanistically, induced expression of clbn suppressed E2F1 activity and down-regulates the DNA replication and expression of its downstream target cyclin E, a key regulator of G1-to-S transition. Meanwhile, clbn over-expression leads to upregulation of the CDK inhibitor Dacapo (Dap), and upregulated Dap is decreased when e2f1 is over-expressed. Furthermore, expression of clbn is down-regulated in cells with e2f1 over-expression or rbf1 knockdown, indicating that Clbn and E2F1 act antagonistically in mediating G1-to-S transition. Thus we provide genetic evidence that Clbn works together with E2F1 in regulating cell cycle progression, and Clbn is required for S phase cell cycle checkpoint in response to DNA damage.
登录
查看更多内容
影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Craighead FL
通讯作者：
Craighead FL