Derheimer Frederick A, Chang Ching-Wei, Ljungman Mats
Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
Eur J Cancer. 2005 Nov;41(16):2569-76. doi: 10.1016/j.ejca.2005.08.012. Epub 2005 Oct 5.
Interference with transcription triggers a stress response leading to the induction of the tumour suppressor p53. If transcription is not restored within a certain time frame cells may undergo apoptosis in a p53-dependent and independent manner. The mechanisms by which blockage of transcription induces apoptosis may involve diminished levels of anti-apoptotic factors, inappropriate accumulation of proteins in the nucleus, accumulation of p53 at mitochondria or complications during replication. Many chemotherapeutic agents currently used in the clinic interfere with transcription and this interference may contribute to their anti-cancer activities. Future efforts should be directed towards exploring whether interference of transcription could be used as an anti-cancer therapeutic strategy.
转录干扰会引发应激反应,导致肿瘤抑制因子p53的诱导。如果转录在一定时间内未恢复,细胞可能会以p53依赖和非依赖的方式发生凋亡。转录受阻诱导凋亡的机制可能包括抗凋亡因子水平降低、蛋白质在细胞核中不当积累、p53在线粒体中积累或复制过程中的并发症。目前临床上使用的许多化疗药物会干扰转录,这种干扰可能有助于它们的抗癌活性。未来的努力应致力于探索转录干扰是否可作为一种抗癌治疗策略。