Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
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E2F3a 和 CASP8AP2 的相互作用调节白血病细胞的组蛋白表达和化疗敏感性
DOI：
10.1097/mph.0000000000002558
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发表时间：
2023-04-01
影响因子：
1.2
通讯作者：
Li, Zhi-gang
中科院分区：
文献类型：
--
作者：
Jin, Fen-fen;Wang, Chan-juan;Cui, Lei;Liu, Fei-fei;Wang, Kai-ling;Li, Wei-jing;Li, Zhi-gang
E2 F3 a和半胱天冬酶8相关蛋白2（CASP 8AP 2）的低表达水平与急性淋巴细胞白血病儿童的不良预后相关我们先前的研究表明，E2 F3 a和CASP 8AP 2表达的联合评估在预测急性淋巴细胞白血病儿童复发方面更准确。然而，其潜在机制仍不清楚。在这项研究中，E2 F3 a和CASP 8AP 2之间的相互作用及其在组蛋白表达，细胞增殖，细胞周期和化疗敏感性的调节中的作用进行了研究。在HEK-293 T细胞中，外源性E2 F3 a-GST与CASP 8AP 2-FLAG共沉淀。E2 F3 a与CASP 8AP 2-GFP共定位于细胞核中。在HEK-293 T或697细胞中，E2 F3 a或CASP 8AP 2过表达时，复制依赖性组蛋白H2 A和H2 B显著上调，而E2 F3 a或CASP 8AP 2敲低则下调。E2 F3 a和CASP 8AP 2可协同增强HIST 1H 2AG和HIST 1H 2BK的转录活性。CASP 8AP 2和E2 F3 a均参与S期进展。E2 F3 a和CASP 8AP 2也影响白血病细胞对柔红霉素的敏感性。因此，CASP 8AP 2和E2 F3 a协同调节白血病细胞的复制依赖性组蛋白表达、细胞周期进程和化疗敏感性。
Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AG and HIST1H2BK. Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.
影响因子：
3.7
作者：
Chen S;Evans HG;Evans DR
通讯作者：
Evans DR
影响因子：
3.7
作者：
Minamida Y;Someda M;Yonehara S
通讯作者：
Yonehara S