Identification of proteins suppressing the functions of oncogenic phosphatase of regenerating liver 1 and 3
Identification of proteins suppressing the functions of oncogenic phosphatase of regenerating liver 1 and 3
复制标题
DOI：
10.3892/etm.2016.3722
复制
发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Min, Sang-Hyun
中科院分区：
文献类型：
--
作者：
Lee, Ju-Dong;Jung, Haiyoung;Min, Sang-Hyun
再生肝磷酸酶（PRL）家族，包括PRL-1、PRL-2和PRL-3，包括蛋白酪氨酸磷酸酶，其失调与许多类型癌症的肿瘤发生和转移相关。然而，对潜在的机制知之甚少。本研究利用酵母双杂交系统筛选PRL-1和PRL-3的相互作用蛋白，旨在进一步了解PRL-1和PRL-3的分子机制。与NCBI BLAST数据库的比对揭示了12种相互作用的蛋白质：突触核包膜蛋白2、emerin、甘露糖6-磷酸受体结合蛋白1、低密度脂蛋白受体相关蛋白10、Rab受体1、肿瘤蛋白D52样2、选择素P配体（SELPLG）、鸟苷酸结合蛋白1、含跨膜和泛素样结构域2、NADH：泛醌氧化还原酶亚基B8、多配体蛋白聚糖4和FK 506结合蛋白8（FKBP 8）。这些蛋白质在生物学过程类别中与细胞增殖、凋亡、免疫应答、细胞命运指定和代谢过程相关，并参与多种信号通路，包括阿尔茨海默病、帕金森病、亨廷顿病、肥厚型心肌病和细胞粘附分子。PRL-1与猎物蛋白SELPLG和FKBP 8的相互作用通过免疫沉淀或免疫染色证实。此外，SELPLG和FKBP 8抑制PRL-1或PRL-3介导的p53活性。识别与PRL家族蛋白相互作用的蛋白质可能为更好地理解PRL介导的信号转导在癌症和其他多种疾病中的机制提供有价值的信息。
The phosphatase of regenerating liver (PRL) family, including PRL-1, PRL-2, and PRL-3, comprises protein tyrosine phosphatases whose deregulation is associated with the tumorigenesis and metastasis of many types of cancer. However, the underlying mechanism is poorly understood. In this study, aiming to increase understanding of the molecular mechanisms underlying the functions of PRL-1 and PRL-3, a yeast two-hybrid system was employed to screen for their interacting proteins. Alignment with the NCBI BLAST database revealed 12 interactive proteins: Synaptic nuclear envelope protein 2, emerin, mannose 6-phosphate receptor-binding protein 1, low-density lipoprotein receptor-related protein 10, Rab acceptor 1, tumor protein D52-like 2, selectin P ligand (SELPLG), guanylate binding protein 1, transmembrane and ubiquitin-like domain-containing 2, NADH: ubiquinone oxidoreductase subunit B8, syndecan 4 and FK506-binding protein 8 (FKBP8). These proteins are associated with cell proliferation, apoptosis, immune response, cell fate specification and metabolic process in biological process categories, and involved in various signaling pathways, including Alzheimer's disease, Parkinson's disease, Huntington's disease, hypertrophic cardiomyopathy and cell adhesion molecules. Interactions of PRL-1 with the prey proteins SELPLG and FKBP8 were confirmed by immunoprecipitation or immunostaining. Furthermore, SELPLG and FKBP8 suppressed PRL-1- or PRL-3-mediated p53 activity. Identification of the proteins interacting with PRL family proteins may provide valuable information to better understand the mechanism of PRL-mediated signal transduction in cancer and other diverse diseases.