Role of Bag-1 in the survival and proliferation of the cytokine-dependent lymphocyte lines, Ba/F3 and Nb2
Role of Bag-1 in the survival and proliferation of the cytokine-dependent lymphocyte lines, Ba/F3 and Nb2
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DOI：
10.1210/me.11.5.608
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发表时间：
1997-05-01
影响因子：
--
通讯作者：
Reed, JC
中科院分区：
文献类型：
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作者：
Clevenger, CV;Thickman, K;Reed, JC
检查了新鉴定的 Bcl-2 和 Raf-1 结合蛋白 Bag-1 在细胞因子调节的 B 和 T 细胞系生长过程中的表达和功能。对白细胞介素 3 (IL-3) 依赖性 B 细胞系 Ba/F3 和 PRL 依赖性 T 细胞系 Nb2 裂解物的免疫印迹分析表明，Bag-1 水平的变化与生长因子存在或不存在诱导的细胞增殖、活力和凋亡的变化平行。为了测试 Bag-1 水平的上调是否会改变细胞存活和增殖，用 Bag-1 表达构建体转染 Ba/F3 细胞。 Bag-1 在转染的 Ba/F3 细胞中的过度表达诱导了 IL-3 独立状态。在完全不存在外源 IL-3 的情况下，此类转染子表现出持续的活力和增殖，并且细胞凋亡最小。在地塞米松 (Dex) 中培养这些细胞系期间，还比较了糖皮质激素敏感的 Nb2 细胞和不依赖于 PRL 的糖皮质激素抗性亚系 SFJCD1 中的 Bag-1 表达。在细胞凋亡开始之前，向 Nb2 细胞中添加 Dex 会显着降低 Bag-1 水平。相比之下，Dex 治疗或 PRL 撤除对 SFJCD1 系内的 Bag-1 水平没有影响。这些发现证实，Bag-1 在适当的细胞环境中过度表达可促进细胞存活和生长，这些事件可能是由于该蛋白与促有丝分裂和抗凋亡信号通路并置所致。
The expression and function of the newly identified Bcl-2- and Raf-1- binding protein, Bag-1, during the cytokine-regulated growth of B and T cell lines was examined. Immunoblot analysis of lysates from the interleukin-3 (IL-3)-dependent B cell line Ba/F3, and the PRL-dependent T cell line Nb2, revealed that variations in Bag-1 levels paralleled alterations in cellular proliferation, viability, and apoptosis induced by the presence or absence of growth factor. To test whether up-regulation of Bag-1 levels altered cellular survival and proliferation, Ba/F3 cells were transfected with a Bag-1 expression construct. The overexpression of Bag-1 in transfected Ba/F3 cells induced an IL-3-independent state. Such transfectants demonstrated sustained viability and proliferation, with minimal apoptosis, in the complete absence of exogenous IL-3. Bag-1 expression was also compared in glucocorticoid-sensitive Nb2 cells and a PRL-independent, glucocorticoid-resistant subline, SFJCD1, during culture of these lines in dexamethasone (Dex). Bag-1 levels were profoundly decreased by the addition of Dex to Nb2 cells, precedent to the onset of apoptotic cell death. In contrast, Dex treatment or PRL withdrawal had no effect on levels of Bag-1 within the SFJCD1 line. These findings establish that the overexpression of Bag-1 in the appropriate cellular context promotes cellular survival and growth, events that may result from the juxtaposition of this protein with mitogenic and antiapoptotic signaling pathways.