Mass spectroscopy analysis of Nuclear YAP1 interacting proteins

YAP1 regulates the expression of several genes involved in diverse cell biology, including cell growth, cell survival, cell differentiation, cell transformation, carcinogenesis, and metastasis. In the present study, we employed co-immunoprecipitations combined with mass spectroscopy to identify nuclear YAP1 interacting proteins in the well-established human prostate tumor cell models steroid. Our proteomics analysis demonstrated that androgen hormone signaling regulates the YAP1 interacting proteins. Our functional annotation clustering showed that YAP1-associated proteins were enriched for diverse cellular pathways, including RNA transport, RNA processing, RNA translation, posttranscriptional regulation, protein folding, metabolism, etc. Furthermore, we characterized the molecular and functional interaction between multifunctional, polycomb group protein SCML2 and YAP1 in cultures. Our results demonstrate that YAP1 cooperates with the epigenetic regulatory protein SCML2 to module cell growth, cell survival, and oncogenesis downstream of steroid hormone androgen signaling.YAP1可调控多种参与多样细胞生物学过程的基因表达，涵盖细胞生长、细胞存活、细胞分化、细胞转化、癌变及转移等生物学过程。本研究采用免疫共沉淀（co-immunoprecipitation）结合质谱（mass spectrometry）技术，在已建立的类固醇激素响应型人前列腺肿瘤细胞模型中鉴定核定位YAP1的互作蛋白。蛋白质组学分析结果显示，雄激素信号通路可调控YAP1的互作蛋白谱。功能注释聚类分析表明，YAP1结合蛋白显著富集于多条细胞通路，包括RNA转运、RNA加工、RNA翻译、转录后调控、蛋白质折叠及代谢等。此外，本研究在细胞培养体系中解析了多功能多梳蛋白家族（polycomb group）成员SCML2与YAP1之间的分子与功能互作。本研究结果证实，YAP1与表观遗传调控蛋白SCML2协同作用，在类固醇激素雄激素信号通路下游调控细胞生长、细胞存活及肿瘤发生。