NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.
NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity.
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发表时间：
2004
影响因子：
5.3
通讯作者：
S. Fujioka;Jiangong Niu;C. Schmidt;G. Sclabas;B. Peng;T. Uwagawa;Zhongkui Li;Douglas B. Evans;J. Abbruzzese;P. Chiao
中科院分区：
文献类型：
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作者：
S. Fujioka;Jiangong Niu;C. Schmidt;G. Sclabas;B. Peng;T. Uwagawa;Zhongkui Li;Douglas B. Evans;J. Abbruzzese;P. Chiao
核因子κ b （nf - κ b）和激活蛋白1 （AP-1）转录因子调控着许多重要的生物和病理过程。NF-kappaB的活化是由IkappaB激酶诱导NF-kappaB抑制剂IkappaB磷酸化调控的。相反，作为AP-1的关键成分，Fos主要受血清反应因子（SRFs）和三元复合因子（tcf）的转录调节。尽管存在这些不同的调控机制，但NF-kappaB和AP-1可能相互调节，从而扩大了这两种快速诱导转录因子的范围。为了确定NF-kappaB活性是否参与各种刺激对fos表达的调控，我们利用mdapanc28和mdapanc28 /IkappaBalphaM胰腺肿瘤细胞和野生型、IKK1-/-和IKK2-/-小鼠胚胎成纤维细胞，分析了AP-1活性和fos、fosB、fra-1、fra-2、jun、junB、junD以及AP-1下游靶基因VEGF的表达。结果表明，作为tcf成员的elk-1是NF-kappaB下游靶基因之一。抑制NF-kappaB活性可显著降低elk-1的表达。因此，细胞外信号调节激酶激活的Elk-1蛋白水平的降低阻碍了组成型、血清型和超氧化物诱导的c-fos表达。因此，我们的研究揭示了NF-kappaB在参与调控elk-1、c-fos和VEGF表达中的独特而重要的作用。
Nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-kappaB is regulated by the inducible phosphorylation of NF-kappaB inhibitor IkappaB by IkappaB kinase. In contrast, Fos, a key component of AP-1, is primarily transcriptionally regulated by serum responsive factors (SRFs) and ternary complex factors (TCFs). Despite these different regulatory mechanisms, there is an intriguing possibility that NF-kappaB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-kappaB activity is involved in the regulation of fos expression in response to various stimuli, we analyzed activity of AP-1 and expression of fos, fosB, fra-1, fra-2, jun, junB, and junD, as well as AP-1 downstream target gene VEGF, using MDAPanc-28 and MDAPanc-28/IkappaBalphaM pancreatic tumor cells and wild-type, IKK1-/-, and IKK2-/- murine embryonic fibroblast cells. Our results show that elk-1, a member of TCFs, is one of the NF-kappaB downstream target genes. Inhibition of NF-kappaB activity greatly decreased expression of elk-1. Consequently, the reduced level of activated Elk-1 protein by extracellular signal-regulated kinase impeded constitutive, serum-, and superoxide-inducible c-fos expression. Thus, our study revealed a distinct and essential role of NF-kappaB in participating in the regulation of elk-1, c-fos, and VEGF expression.