Regulation of drug sensitivity by ribosomal protein S3a
Regulation of drug sensitivity by ribosomal protein S3a
复制标题
DOI：
10.1182/blood.v95.3.1047.003k43_1047_1055
复制
发表时间：
2000-02-01
期刊：
影响因子：
20.3
通讯作者：
McCulloch, EA
中科院分区：
文献类型：
--
作者：
Hu, ZB;Minden, MD;McCulloch, EA
当从全反式维甲酸（ATRA）处理的急性髓母细胞白血病（AML）细胞的p -32标记的细胞提取物中免疫沉淀bcl-2时，共沉淀出约30 kd的磷酸化蛋白，该蛋白已被鉴定为核糖体蛋白S3a， S3a的生物学效应包括促进细胞凋亡和增强恶性表型。我们试图确定S3a是否像bcl-2一样影响细胞对化疗药物和ATRA的反应。研究了S3a基因增加或中断的细胞系；增加的S3a与增加的镀金效率和对阿拉伯糖胞嘧啶（ara-C）或多柔比星（DNR）的敏感性有规律地相关，S3a不影响细胞对紫杉醇的敏感性，脉冲暴露于(3)HTdR或ara-C的细胞中，S3a增加的细胞在细胞周期的S期的克隆细胞百分比高于对照组。S3a蛋白增加的细胞对ATRA的反应是增加ara-C或DNR的敏感性，而S3a蛋白减少的细胞要么受到ATRA的保护，要么不受影响。我们研究了AML或慢性髓单细胞白血病（CMML）患者的冷冻保存母细胞，这些人群的S3a蛋白水平是异质的。在32个冷冻保存的细胞群体中，S3a水平与bcl-2和培养细胞的生长均显著相关。在细胞系中，高水平的S3a与atra诱导的ara-C致敏相关，S3a水平与治疗反应无显著关联。(C) 2000年由美国血液学会出版。
When bcl-2 is immunoprecipitated from P-32-labeled cell extracts of all-trans retinoic acid (ATRA)-treated acute myeloblastic leukemia (AML) blasts, a phosphorylated protein of approximately 30 kd is coprecipitated, This protein has been identified as ribosomal protein S3a, The biologic effects of S3a include favoring apoptosis and enhancing the malignant phenotype. We sought to determine whether S3a, like bcl-2, influenced the response of cells to chemotherapeutic drugs and ATRA. Cell lines were studied in which S3a was genetically increased or disrupted; increased S3a was regularly associated with increased plating efficiency and increased sensitivity to either cytosine arabinoside (ara-C) or doxorubicin (DNR), S3a did not affect the sensitivity of cells to paclitaxel, Pulse exposures to either (3)HTdR or ara-C showed a greater percentage of clonogenic cells in the S phase of the cell cycle in cells with increased S3a than in controls. Cells with increased S3a responded to ATRA by increased ara-C or DNR sensitivity, whereas cells with reduced S3a protein were either protected by ATRA or not affected. We studied cryopreserved blast cells from patients with AML or chronic myelomonocytic leukemia (CMML), S3a protein levels were heterogeneous in these populations. In 32 cryopreserved blast populations, S3a levels were significantly correlated with both bcl-2 and with cell growth in culture. As in cell lines, high S3a in cryopreserved blasts was associated with ATRA-induced sensitization to ara-C, No significant association was seen between S3a levels and response to treatment.(C) 2000 by The American Society of Hematology.