YAP1与多梳蛋白家族蛋白SCML2之间的不协调相互作用决定细胞命运。
Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate.
作者信息
Boston Ava M, Dwead Abdulrahman M, Al-Mathkour Marwah M, Khazaw Kezhan, Zou Jin, Zhang Qiang, Wang Guangdi, Cinar Bekir
机构信息
Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA.
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA.
出版信息
iScience. 2023 Sep 20;26(10):107964. doi: 10.1016/j.isci.2023.107964. eCollection 2023 Oct 20.
The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones.
多梳蛋白组蛋白SCML2和转录辅因子YAP1调节多种细胞生物学过程，包括哺乳动物和果蝇中的干细胞维持、发育过程以及基因调控。然而，它们的分子和功能相互作用尚不清楚。在这里，我们通过免疫分析和质谱表明，SCML2与YAP1相互作用。我们已经证明，在人类肿瘤细胞模型中，类固醇激素雄激素调节SCML2与YAP1的相互作用。我们的邻近连接分析和谷胱甘肽S-转移酶下拉实验表明，SCML2和YAP1彼此发生物理相互作用。通过RNA干扰使SCML2沉默改变了细胞对雄激素信号的生长反应。从机制上讲，这种现象归因于不同染色质修饰和转录程序之间的相互作用，可能由相反的SCML2和YAP1活性协调。这些发现表明，YAP1和SCML2协同调节类固醇激素下游的细胞生长、细胞存活和肿瘤生物学。
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