Cancer‑testis antigen HCA587/MAGEC2 interacts with the general transcription coactivator TAF9 in cancer cells.
Cancer‑testis antigen HCA587/MAGEC2 interacts with the general transcription coactivator TAF9 in cancer cells.
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DOI：
10.3892/mmr.2017.8260
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
P. Zeng;Ying Wang;Yutian Zheng;Xiao Song;Yanhui Yin
中科院分区：
文献类型：
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作者：
P. Zeng;Ying Wang;Yutian Zheng;Xiao Song;Yanhui Yin
肝细胞癌相关抗原587/黑色素瘤抗原基因（HCA587/MAGEC2）是一种癌睾丸抗原，在各种类型的肿瘤中高表达，但在除男性生殖细胞外的正常组织中不表达。 HCA587/MAGEC2 此前已被认为是免疫治疗的肿瘤特异性靶点；然而，其生物学功能的研究相对较少。为了研究HCA587/MAGEC2的功能，通过生物信息学分析了HCA587/MAGEC2的氨基酸序列，证明HCA587/MAGEC2含有9个氨基酸的反式激活结构域，该结构域可能介导大多数转录因子与通用转录共激活因子TATA-box结合蛋白相关因子9（TAF9）的相互作用。免疫共沉淀实验表明，在转染的293T和内源表达HCA587/MAGEC2的A375黑色素瘤细胞中，HCA587/MAGEC2与TAF9相互作用，并证实了细胞内HCA587/MAGEC2和TAF9的内源相互作用。使用免疫荧光证明内源性 HCA587/MAGEC2 和 TAF9 主要共定位于肿瘤细胞的细胞核中。谷胱甘肽-S-转移酶下拉实验表明，HCA587/MAGEC2 直接与 TAF9 相互作用，并且 TAF9 中的保守区域可能对于 HCA587/MAGEC2 结合至关重要。本研究表明，癌睾丸抗原 HCA587/MAGEC2 直接与 TAF9 相互作用，这可能为鉴定 HCA587/MAGEC2 在肿瘤细胞中的致癌功能提供新的信息。
Hepatocellular carcinoma-associated antigen 587/melanoma antigen gene (HCA587/MAGEC2) is a cancer‑testis antigen, which is highly expressed in various types of tumors, but not in normal tissues with the exception of male germ‑line cells. HCA587/MAGEC2 has been previously recognized as a tumor‑specific target for immunotherapy; however, its biological functions have been relatively understudied. To investigate the function of HCA587/MAGEC2, the amino acid sequence of HCA587/MAGEC2 was analyzed by bioinformatics and it was demonstrated that HCA587/MAGEC2 contains a 9‑amino acid transactivation domain which may mediate the interaction of most transcription factors with TATA‑box binding protein associated factor 9 (TAF9), a general transcription coactivator. Co‑immunoprecipitation experiments revealed that HCA587/MAGEC2 interacted with TAF9 in transfected 293T and in A375 melanoma cells endogenously expressing HCA587/MAGEC2, and confirmed the endogenous interaction of HCA587/MAGEC2 and TAF9 within cells. Endogenous HCA587/MAGEC2 and TAF9 were demonstrated to be co‑localized principally in the nucleus of tumor cells using immunofluorescence. Glutathione-S-transferase pull‑down experiments demonstrated that HCA587/MAGEC2 interacts with TAF9 directly and the conserved region in the TAF9 may becrucial for HCA587/MAGEC2 binding. The present study demonstrated that the cancer‑testis antigen HCA587/MAGEC2 directly interacted with TAF9, which may provide novel information for identifying the oncogenic functions of HCA587/MAGEC2 in tumor cells.