Protein kinase ATR inhibits E3 ubiquitin ligase CRL4PRL1 to stabilize ribonucleotide reductase in response to replication stress
Protein kinase ATR inhibits E3 ubiquitin ligase CRL4PRL1 to stabilize ribonucleotide reductase in response to replication stress
复制标题
DOI：
10.1016/j.celrep.2023.112685
复制
发表时间：
2023-06-23
期刊：
影响因子：
8.8
通讯作者：
Yan，Shunping
中科院分区：
文献类型：
--
作者：
Bao，Weiyi;Zhang，Weijia;Yan，Shunping
蛋白激酶ATR是所有真核生物复制应激反应所必需的。核糖核苷酸还原酶（RNR）催化脱氧核糖核苷酸（dNTP）的形成，脱氧核糖核苷酸是DNA复制和修复的通用构件。然而，ATR和RNR之间的关系并不清楚。在这里，我们表明，ATR促进拟南芥中的RNR蛋白质的稳定性。通过基于激活标记的遗传筛选，我们发现过表达RNR的一个小亚基TSO 2，部分抑制了theatrmutant对复制应激的超敏反应。在生物化学上，TSO 2与PRL 1相互作用，PRL 1是基于Cullin 4的E3泛素连接酶CRL 4PRL 1的中心亚基，其聚泛素化TSO 2并促进其降解。ATR通过抑制CRL 4 PRL 1的表达，抑制TSO 2的降解。我们的工作为RNR的复制应激反应和翻译后调控机制提供了重要的见解。考虑到所涉及的蛋白质的进化保守性，ATR-PRL 1-RNR模块可能在真核生物中起作用。
The protein kinase ATR is essential for replication stress responses in all eukaryotes. Ribonucleotide reductase (RNR) catalyzes the formation of deoxyribonucleotide (dNTP), the universal building block for DNA replication and repair. However, the relationship between ATR and RNR is not well understood. Here, we show that ATR promotes the protein stability of RNR in Arabidopsis. Through an activation tagging-based genetic screen, we found that overexpression of TSO2, a small subunit of RNR, partially suppresses the hypersensitivity of theatrmutant to replication stress. Biochemically, TSO2 interacts with PRL1, a central subunit of the Cullin4-based E3 ubiquitin ligase CRL4PRL1, which polyubiquitinates TSO2 and promotes its degradation. ATR inhibits CRL4PRL1to attenuate TSO2 degradation. Our work provides an important insight into the replication stress responses and a post-translational regulatory mechanism for RNR. Given the evolutionary conservation of the proteins involved, the ATR-PRL1-RNR module may act across eukaryotes.
影响因子：
7.4
作者：
Tulin F
通讯作者：
Tulin F
影响因子：
5.5
作者：
Matos-Rodrigues GE;Martins RAP
通讯作者：
Martins RAP
影响因子：
5.6
作者：
Eekhout T;Pedroza-Garcia JA;Kalhorzadeh P;De Jaeger G;De Veylder L
通讯作者：
De Veylder L