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甲精介导核内激动蛋白在雄激素受体处促进转录
作者:小柯机器人 发布时间:2023/3/31 14:41:57

德国吕贝克大学Nadine C. Hornig等研究人员合作发现,甲精介导核内激动蛋白在雄激素受体处促进转录。相关论文于2023年3月27日在线发表在《自然》杂志上。

研究人员表示,类固醇激素受体是配体结合的转录因子,对哺乳动物的生理学至关重要。雄性激素受体(AR)与雄性激素结合,介导性、体细胞和行为功能的基因表达,并涉及各种健康状况,包括雄性激素不敏感综合征(AIS)或前列腺癌。

研究人员确定了AIS患者在甲精和肌动蛋白成核子DAAM2的功能性突变。DAAM2在细胞核中富集,它的定位与AR相关,并形成依赖肌动蛋白的转录液滴,以响应二氢睾酮。DAAM2-AR-液滴的大小为0.02至0.06 µm3,与活跃的RNA聚合酶II相关。DAAM2直接在AR处聚合肌动蛋白,以高度动态的方式促进液滴凝聚,核内肌动蛋白聚合是癌细胞中前列腺特异性抗原表达所需的。这些数据揭示了转录所需的类固醇激素受体的信号调节核内肌动蛋白的组装。

附:英文原文

Title: Formin-mediated nuclear actin at androgen receptors promotes transcription

Author: Knerr, Julian, Werner, Ralf, Schwan, Carsten, Wang, Hong, Gebhardt, Peter, Grtsch, Helga, Caliebe, Almuth, Spielmann, Malte, Holterhus, Paul-Martin, Grosse, Robert, Hornig, Nadine C.

Issue&Volume: 2023-03-27

Abstract: Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic, and behavioral functions, and is involved in various conditions including androgen-insensitivity-syndrome (AIS) or prostate cancer 1. Here we identified functional AIS-patient mutations in the formin and actin nucleator DAAM2. DAAM2 was enriched in the nucleus, where its localization correlated with that of the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2-AR-droplets ranged from 0.02 to 0.06 μm3 in size and associated with active RNA polymerase II. DAAM2 polymerized actin directly at the AR to promote droplet coalescence in a highly dynamic manner and nuclear actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.

DOI: 10.1038/s41586-023-05981-1

Source: https://www.nature.com/articles/s41586-023-05981-1

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html

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