AP-1 activity affects the levels of induced erythroid and megakaryocytic differentiation of K562 cells.
AP-1 activity affects the levels of induced erythroid and megakaryocytic differentiation of K562 cells.
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DOI：
10.1006/abbi.1998.0597
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发表时间：
1998-04
影响因子：
3.9
通讯作者：
Dan Rosson;Thomas G. O'Brien
中科院分区：
文献类型：
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作者：
Dan Rosson;Thomas G. O'Brien
检测了调节AP-1活性对红白血病细胞系K562的诱导红系和巨核细胞分化水平的影响。用编码四环素应答显性阴性c-Jun（JunDN）或雌激素诱导的杂合Raf蛋白的表达载体稳定转染细胞。通过诱导JunDN下调AP-1活性增强了两种试剂（阿糖胞苷和激活素A）的红系分化。由Raf活性升高引起的AP-1活性的诱导抑制了红系分化，从而模仿了十四烷酰基佛波醇乙酸酯（TPA）对该过程的众所周知的作用。诱导的Raf活性也导致了该细胞系的部分巨核细胞分化。然而，通过诱导JunDN抑制TPA诱导的AP-1活性得到了混合的结果。虽然TPA处理对细胞化学染色观察到的细胞学效应被JunDN抑制，但巨核细胞分化的两种蛋白质标记物增加。这些结果，虽然支持目前的造血谱系特异性基因表达的模型，提示一个复杂的和时间的谱系承诺机制。
The effect of modulating AP-1 activity on the levels of induced erythroid and megakaryocytic differentiation of the erythroleukemia cell line K562 was examined. Cells were stably transfected with expression vectors encoding either a tetracycline-responsive dominant negative c-Jun (JunDN) or a hybrid Raf protein inducible by estrogen. Down-regulation of AP-1 activity by induction of JunDN enhanced erythroid differentiation by two agents, cytosine arabinoside and activin A. Induction of AP-1 activity by elevated Raf activity inhibited erythroid differentiation, thus mimicking the well-known effect of tetradecanoyl phorbol acetate (TPA) on this process. Induced Raf activity also brought about partial megakaryocytic differentiation of the line. However, inhibition of TPA-induced AP-1 activity by induction of JunDN gave mixed results. While the cytological effects of TPA treatment observed on cytochemical staining were inhibited by JunDN, two protein markers for megakaryocytic differentiation were increased. These results, while supportive of current models of hematopoietic lineage-specific gene expression, suggest a complex and temporal mechanism of lineage commitment.