Skarżyńska Weronika, Baran Brygida, Niewiadomski Paweł
Centre of New Technologies, University of Warsaw, Warsaw, Poland.
Faculty of Biology, University of Warsaw, Warsaw, Poland.
Sci Rep. 2025 Jan 2;15(1):324. doi: 10.1038/s41598-024-83468-3.
Regulation of the Hedgehog pathway activity may be supported by coactivators and corepresors of its main effectors- Gli transcription factors. While activation processes are well studied, repression mechanisms remain elusive. We identified chromatin remodelling complex Hira to interact with Gli3R protein, showed that its loss-of-function changes Hh pathway activity, and examined possible mechanism behind the observed effect. We also established that Hira influences the viability and migratory abilities of Hh-dependent medulloblastoma Daoy cells. Our study paves the way for a better understanding of processes involved in Hh pathway regulation and Hh-dependent carcinogenesis.
刺猬信号通路活性的调节可能由其主要效应物Gli转录因子的共激活因子和共抑制因子来支持。虽然激活过程已得到充分研究,但抑制机制仍不清楚。我们鉴定出染色质重塑复合体Hira与Gli3R蛋白相互作用,表明其功能丧失会改变Hh信号通路活性,并研究了观察到的效应背后的可能机制。我们还确定Hira会影响Hh依赖的髓母细胞瘤Daoy细胞的活力和迁移能力。我们的研究为更好地理解Hh信号通路调节和Hh依赖的致癌作用所涉及的过程铺平了道路。