AP1 regulation of proliferation and initiation of apoptosis in erythropoietin-dependent erythroid cells
AP1 regulation of proliferation and initiation of apoptosis in erythropoietin-dependent erythroid cells
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DOI：
10.1128/mcb.18.7.3699
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发表时间：
1998-07-01
影响因子：
5.3
通讯作者：
Sawyer, ST
中科院分区：
文献类型：
--
作者：
Jacobs-Helber, SM;Wickrema, A;Sawyer, ST
转录因子AP 1与细胞响应于应激因子和生长因子撤除而诱导细胞凋亡有关。我们在这里报告，AP 1是必要的诱导凋亡后激素撤退的促红细胞生成素（EPO）依赖性红细胞系HCD 57。从EPO中撤出HCD 57细胞后，AP 1 DNA结合活性增加。显性负性AP 1突变体使这些细胞对EPO停药诱导的凋亡具有抵抗性，并阻断Bcl-X-L的下调。JunB是EPO停药后观察到的API复合物中的主要结合蛋白;在HCD 57细胞中，EPO停药后3小时，JunB而不是c-Jun存在于AP 1复合物中，同时JunB信息和蛋白质增加。此外，在HCD 57的抗肿瘤亚克隆中的API DNA结合活性的分析揭示了在EPO撤除后缺乏对AP 1 DNA结合活性的诱导，并且junB mRNA水平没有变化。此外，我们确定c-Jun和AP 1活性与EPO诱导的增殖和/或保护凋亡相关。EPO刺激HCD 57细胞后的前3小时内，AP 1 DNA结合活性增加，抑制AP 1活性部分抑制EPO诱导的增殖。EPO加入后3小时，AP 1复合物中存在c-Jun，但不存在JunB。这些结果暗示AP 1在红系细胞的增殖和存活的调节中，并且表明不同的API因子可能在触发凋亡（JunB）和保护红系细胞免于凋亡（c-Jun）两者中发挥不同的作用。
The transcription factor AP1 has been implicated in the induction of apoptosis in cells in response to stress factors and growth factor withdrawal. We report here that AP1 is necessary for the induction of apoptosis following hormone withdrawal in the erythropoietin (EPO)-dependent erythroid cell line HCD57. AP1 DNA binding activity increased upon withdrawal of HCD57 cells from EPO. A dominant negative AP1 mutant rendered these cells resistant to apoptosis induced by EPO withdrawal and blocked the downregulation of Bcl-X-L. JunB is a major binding protein in the API complex observed upon EPO withdrawal; JunB but not c-Jun was present in the AP1 complex 3 h after EPO withdrawal in HCD57 cells, with a concurrent increase in junB message and protein. Furthermore, analysis of API DNA binding activity in an apoptosis-resistant subclone of HCD57 revealed a lack of induction in AP1 DNA binding activity and no change in junB mRNA levels upon EPO withdrawal. In addition, we determined that c-Jun and AP1 activities correlated with EPO-induced proliferation and/or protection from apoptosis. AP1 DNA binding activity increased over the first 3 h following EPO stimulation of HCD57 cells, and suppression of AP1 activity partially inhibited EPO-induced proliferation. c-Jun but not JunB was present in the AP1 complex 3 h after EPO addition. These results implicate AP1 in the regulation of proliferation and survival of erythroid cells and suggest that different API factors may play distinct roles in both triggering apoptosis (JunB) and protecting erythroid cells from apoptosis (c-Jun).