MAINTENANCE OF NF-KAPPA-B ACTIVITY IS DEPENDENT ON PROTEIN-SYNTHESIS AND THE CONTINUOUS PRESENCE OF EXTERNAL STIMULI
MAINTENANCE OF NF-KAPPA-B ACTIVITY IS DEPENDENT ON PROTEIN-SYNTHESIS AND THE CONTINUOUS PRESENCE OF EXTERNAL STIMULI
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DOI：
10.1128/mcb.11.1.259
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发表时间：
1991-01-01
影响因子：
5.3
通讯作者：
VANLOON, APGM
中科院分区：
文献类型：
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作者：
HOHMANN, HP;REMY, R;VANLOON, APGM
比较肿瘤坏死因子-α(TNF-α)和佛波酯-12-肉豆蔻酸13-醋酸酯(PMA)对核因子-kappa-B样活性(称为核因子-kappaB)的激活作用。在肿瘤坏死因子-α作用于人HL60细胞2~4min后，发现高水平的核因子-kappa-B活性，并持续至少3h，但活性核因子-kappaB的半衰期不到30min。然而，非活性的核因子-kappaB相对稳定。由肿瘤坏死因子-α激活的核因子-kappa-B最初是环己亚胺不敏感的，但维持核因子-kappa-B的活性需要持续的蛋白质合成和肿瘤坏死因子-α的持续刺激。因此，在没有刺激的情况下，细胞不会保持激活状态。在HL60细胞中，PMA诱导的NF-kappa-B活性需要30~45min，且完全依赖于从头合成的蛋白质，而PMA(和IL-1)通过非蛋白质合成的机制快速诱导小鼠70z/3细胞中的NF-kappa-B活性。在甲基化干扰和天然蛋白降解指纹图谱分析中，每种条件下获得的核因子-kappa-B样活性表现一致。因此，诱导的核因子-kappa-B样因子都非常相似或完全相同。我们认为，蛋白激酶C依赖的核因子-kappaB的激活可能存在细胞特异性差异，肿瘤坏死因子-α和PMA可能诱导编码核因子-kappa-B的基因(S)的表达。
The activation of NF-kappa-B-like activities (called NF-kappa-B) by tumor necrosis factor alpha (TNF-alpha) and the phorbol ester phorbol 12-myristate 13-acetate (PMA) were compared. High levels of NF-kappa-B activity were found 2 to 4 min after TNF-alpha addition to human HL60 cells and lasted for at least 3 h, although the half-life of active NF-kappa-B was less than 30 min. Inactive NF-kappa-B, however, was relatively stable. NF-kappa-B activation by TNF-alpha was initially cycloheximide insensitive, but maintenance of NF-kappa-B activity required ongoing protein synthesis and continuous stimulation by TNF-alpha. Thus, the cells did not remain in an activated state without stimulation. In HL60 cells, NF-kappa-B induction by PMA required 30 to 45 min and was completely dependent on de novo protein synthesis, while PMA (and interleukin-1) induced NF-kappa-B activity rapidly in mouse 70Z/3 cells via a protein synthesis-independent mechanism. The NF-kappa-B-like activities obtained under each condition behaved identically in methylation interference and native proteolytic fingerprinting assays. The NF-kappa-B-like factors induced are thus all very similar or identical. We suggest that cell-specific differences in the protein kinase C-dependent activation of NF-kappa-B may exist and that TNF-alpha and PMA may induce expression of the gene(s) encoding NF-kappa-B.