Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics.
Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics.
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通过亲和蛋白质组学鉴定翻译控制的肿瘤蛋白促进癌细胞 DNA 同源重组修复
DOI：
10.1038/onc.2017.289
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发表时间：
2017-12-14
期刊：
影响因子：
8
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Li Y;Sun H;Zhang C;Liu J;Zhang H;Fan F;Everley RA;Ning X;Sun Y;Hu J;Liu J;Zhang J;Ye W;Qiu X;Dai S;Liu B;Xu H;Fu S;Gygi SP;Zhou C
翻译控制肿瘤蛋白（TCTP）参与细胞凋亡、DNA修复和耐药性的调节。然而，基本的分子机制是不明确的。为了更好地了解TCTP参与细胞过程的分子机制，我们进行了基于亲和纯化的蛋白质组学分析，以确定在人宫颈癌HeLa细胞中与TCTP相互作用的蛋白质。我们发现一组参与DNA修复的蛋白质在潜在的TCTP相互作用组中富集。短发夹RNA沉默乳腺癌MCF-7细胞中TCTP导致GFP-Pem 1报告基因DNA双链断裂的同源重组修复效率下降，γ H2 AX和Rad 51灶在电离辐射后持续激活和滞留时间延长。相互免疫沉淀表明，TCTP与Rad 51在体内形成复合物，并且Rad 51的稳定性维持需要TCTP在正常细胞培养条件下在MCF-7细胞中。此外，舍曲林处理使TCTP失活可增强UVC辐射诱导的MCF-7细胞凋亡，并导致对DNA损伤药物依托泊苷和DNA修复抑制剂奥拉帕尼的致敏作用。因此，我们已经确定了一个重要的作用，TCTP在促进DNA双链断裂修复，通过促进DNA同源重组过程，并强调了巨大的潜力，TCTP作为一个药物靶点，以加强传统的化疗与高水平的TCTP表达的癌症患者。
Translationally controlled tumor protein (TCTP) has been implicated in the regulation of apoptosis, DNA repair and drug resistance. However, the underlying molecular mechanisms are poorly defined. To better understand the molecular mechanisms underlying TCTP involved in cellular processes, we performed an affinity purification-based proteomic profiling to identify proteins interacting with TCTP in human cervical cancer HeLa cells. We found that a group of proteins involved in DNA repair are enriched in the potential TCTP interactome. Silencing TCTP by short hairpin RNA in breast carcinoma MCF-7 cells leads to the declined repair efficiency for DNA double-strand breaks on the GFP-Pem1 reporter gene by homologous recombination, the persistent activation and the prolonged retention of γH2AX and Rad51 foci following ionizing radiation. Reciprocal immunoprecipitations indicated that TCTP forms complexes with Rad51 in vivo, and the stability maintenance of Rad51 requires TCTP in MCF-7 cells under normal cell culture conditions. Moreover, inactivation of TCTP by sertraline treatment enhances UVC irradiation-induced apoptosis in MCF-7 cells, and causes sensitization to DNA-damaging drug etoposide and DNA repair inhibitor olaparib. Thus, we have identified an important role of TCTP in promoting DNA double-stand break repair via facilitating DNA homologous recombination processes and highlighted the great potential of TCTP as a drug target to enhance conventional chemotherapy for cancer patients with high levels of TCTP expression.
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影响因子：
--
作者：
Li T;Liu X;Jiang L;Manfredi J;Zha S;Gu W
通讯作者：
Gu W
影响因子：
12.4
作者：
Baylot, Virginie;Katsogiannou, Maria;Rocchi, Palma
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Rocchi, Palma
影响因子：
4.8
作者：
Low, Ley-Hian;Chow, Yuh-Lit;Tan, Seong-Seng
通讯作者：
Tan, Seong-Seng
影响因子：
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作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
16.6
作者：
Hong, Sung-Tae;Choi, Kwang-Wook
通讯作者：
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