Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1
Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1
复制标题
鉴定 DNA 依赖性蛋白激酶催化亚基作为淋巴细胞增强因子 1 的新型相互作用伴侣
DOI：
10.1007/s00795-012-0002-z
复制
发表时间：
2013
影响因子：
1.8
通讯作者：
Senda T
中科院分区：
文献类型：
--
作者：
Shimomura A;Takasaki A;Nomura R;Hayashi N;Senda T
淋巴细胞增强因子 1 (LEF1) 是高迁移率族域转录因子的 LEF/T 细胞特异性因子 (TCF) 家族的成员，在经典 Wnt 信号传导中发挥下游作用。 LEF1 的异常反式激活导致结肠肿瘤、皮脂腺皮肤肿瘤和淋巴细胞白血病的肿瘤发生。 LEF1 相关蛋白对于调节其转录活性至关重要。在这项研究中，谷胱甘肽-S-转移酶下拉测定和质谱分析能够鉴定 DNA 依赖性蛋白激酶催化亚基 (DNA-PKcs) 作为 LEF1 的新型相互作用伙伴。 LEF1 和 DNA-PKcs 之间的相互作用通过体内免疫共沉淀得到证实。此外，双重免疫荧光观察表明，LEF1 和 DNA-PKcs 共定位于结肠腺癌细胞系的细胞核中。 LEF1 和 DNA-PKcs 之间相互作用的鉴定可能为癌症治疗的新疗法以及理解 LEF1 介导的转录调控提供线索。
Lymphocyte enhancer factor 1 (LEF1), a member of the LEF/T-cell-specific factor (TCF) family of the high mobility group domain transcription factors, acts downstream in canonical Wnt signaling. Aberrant transactivation of LEF1 contributes to the tumorigenesis of colonic neoplasms, sebaceous skin tumors, and lymphoblastic leukemia. LEF1-associated proteins are crucial for regulating its transcriptional activity. In this study, glutathione-S-transferase pull-down assay and mass spectrometry enabled identification of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel interaction partner for LEF1. The interaction between LEF1 and DNA-PKcs was confirmed using in vivo co-immunoprecipitation. Furthermore, double immunofluorescence observations showed that LEF1 and DNA-PKcs colocalized in the nuclei of colon adenocarcinoma cell lines. Identification of the interaction between LEF1 and DNA-PKcs may provide clues for a novel therapy for cancer treatment as well as for understanding LEF1-mediated transcriptional regulation.