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。
Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
机构信息
Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematologic Diseases Laboratory, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health.
Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, China.
出版信息
J Pediatr Hematol Oncol. 2023 Apr 1;45(3):e339-e344. doi: 10.1097/MPH.0000000000002558. Epub 2022 Sep 22.
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.
E2F3a 和 caspase 8 相关蛋白 2（CASP8AP2）的低表达水平与儿童急性淋巴细胞白血病的不良预后相关。我们之前的研究表明，联合评估 E2F3a 和 CASP8AP2 的表达水平，更能准确预测儿童急性淋巴细胞白血病的复发。然而，其潜在机制尚不清楚。在这项研究中，研究了 E2F3a 和 CASP8AP2 之间的相互作用及其对组蛋白表达、细胞增殖、细胞周期和化疗敏感性的调节作用。在 HEK-293T 细胞中外源 E2F3a-GST 与 CASP8AP2-FLAG 共沉淀。E2F3a 在细胞核中与 CASP8AP2-GFP 共定位。当在 HEK-293T 或 697 细胞中过表达 E2F3a 或 CASP8AP2 时，复制依赖性组蛋白 H2A 和 H2B 显著上调，而当 E2F3a 或 CASP8AP2 敲低时下调。E2F3a 和 CASP8AP2 可以协同增强 HIST1H2AG 和 HIST1H2BK 的转录活性。CASP8AP2 和 E2F3a 都参与 S 期进展。E2F3a 和 CASP8AP2 还影响白血病细胞对柔红霉素的敏感性。因此，CASP8AP2 和 E2F3a 协同调节复制依赖性组蛋白表达、细胞周期进程和白血病细胞的化疗敏感性。
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