Koh Siang-Boon
School of Cellular and Molecular Medicine, University of Bristol, UK.
Cell Signal. 2022 Jun;94:110310. doi: 10.1016/j.cellsig.2022.110310. Epub 2022 Mar 16.
Upon DNA damage, complex transduction cascades are unleashed to locate, recognise and repair affected lesions. The process triggers a pause in the cell cycle until the damage is resolved. Even under physiologic conditions, this deliberate interruption of cell division is essential to ensure orderly DNA replication and chromosomal segregation. WEE1 is an established regulatory protein in this vast fidelity-monitoring machinery. Its involvement in the DNA damage response and cell cycle has been a subject of study for decades. Emerging studies have also implicated WEE1 directly and indirectly in other cellular functions, including chromatin remodelling and immune response. The expanding role of WEE1 in pathophysiology is matched by the keen surge of interest in developing WEE1-targeted therapeutic agents. This review summarises WEE1 involvement in the cell cycle checkpoints, epigenetic modification and immune signalling, as well as the current state of WEE1 inhibitors in cancer therapeutics.
在DNA损伤时,复杂的转导级联反应被激活,以定位、识别和修复受影响的损伤。这个过程会引发细胞周期的暂停,直到损伤得到解决。即使在生理条件下,这种对细胞分裂的有意中断对于确保有序的DNA复制和染色体分离也是至关重要的。WEE1是这一庞大的保真监测机制中一种已确定的调节蛋白。它参与DNA损伤反应和细胞周期已经成为几十年来的研究课题。新兴研究还直接或间接地表明WEE1参与了其他细胞功能,包括染色质重塑和免疫反应。WEE1在病理生理学中不断扩大的作用,与开发靶向WEE1的治疗药物的浓厚兴趣相匹配。这篇综述总结了WEE1在细胞周期检查点、表观遗传修饰和免疫信号传导中的作用,以及WEE1抑制剂在癌症治疗中的现状。