Transcriptional coactivation of nuclear factor-κB-dependent gene expression by p300 is regulated by poly(ADP)-ribose polymerase-1
Transcriptional coactivation of nuclear factor-κB-dependent gene expression by p300 is regulated by poly(ADP)-ribose polymerase-1
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DOI：
10.1074/jbc.m307957200
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发表时间：
2003-11-14
影响因子：
4.8
通讯作者：
Hottiger, MO
中科院分区：
文献类型：
--
作者：
Hassa, PO;Buerki, C;Hottiger, MO
核因子κ B（NF-κ B）在炎症和细胞存活相关基因的转录调控中起重要作用。在这项研究中，我们证明了在肿瘤坏死因子α（TNF α）或脂多糖（LPS）处理后，在补充野生型PARP-1的聚（ADP）-核糖聚合酶-1敲除（PARP-1（-/-））细胞中，E1 A抑制NF-κ B依赖性基因表达。PARP-1和p300协同共激活NF-κ B依赖性基因表达以响应TNF α和LPS。此外，PARP-1与p300直接相互作用，并增强NF-κ B1/p50与p300的相互作用。C末端含有PARP-1的催化结构域，但不具有其酶活性，是响应TNF α和LPS通过p300完全转录共激活NF-κ B所必需的。总之，这些结果表明，PARP-1与p300协同作用，并在NF-κ B依赖性基因表达中发挥重要的调节作用。
Nuclear factor kappaB (NF-kappaB) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. In this study, we demonstrated that NF-kappaB-dependent gene expression was inhibited by E1A in poly(ADP)- ribose polymerase-1 knock out (PARP-1 (-/-)) cells complemented with wild type PARP-1 after tumor necrosis factor alpha (TNFalpha) or lipopolysaccharide (LPS) treatment. PARP-1 and p300 synergistically coactivated NF-kappaB-dependent gene expression in response to TNFalpha and LPS. Furthermore, PARP-1 interacted directly with p300 and enhanced the interaction of NF-kappaB1/p50 to p300. The C terminus, harboring the catalytic domain of PARP-1 but not its enzymatic activity, was required for complete transcriptional coactivation of NF-kappaB by p300 in response to TNFalpha and LPS. Together, these results indicate that PARP-1 acts synergistically with p300 and plays an essential regulatory role in NF-kappaB-dependent gene expression.