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希拉复合体在刺猬信号通路中调节Gli3R依赖的转录以及髓母细胞瘤细胞的生长和迁移。

The Hira complex regulates Gli3R-dependent transcription in Hedgehog signaling and medulloblastoma cell growth and migration.

作者信息

Skarżyńska Weronika, Baran Brygida, Niewiadomski Paweł

机构信息

Centre of New Technologies, University of Warsaw, Warsaw, Poland.

Faculty of Biology, University of Warsaw, Warsaw, Poland.

出版信息

Sci Rep. 2025 Jan 2;15(1):324. doi: 10.1038/s41598-024-83468-3.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3f6/11697252/a49fa0018f0c/41598_2024_83468_Fig5_HTML.jpg

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