p53 activates ICAM-1 (CD54) expression in an NF-κB-independent manner
p53 activates ICAM-1 (CD54) expression in an NF-κB-independent manner
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DOI：
10.1093/emboj/cdg157
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发表时间：
2003-04-01
期刊：
影响因子：
11.4
通讯作者：
Papavassiliou, AG
中科院分区：
文献类型：
--
作者：
Gorgoulis, VG;Zacharatos, P;Papavassiliou, AG
细胞间粘附分子-1（ICAM-1）是细胞间相互作用的重要受体，细胞间相互作用是对各种形式损伤反应的中心过程。它的表达上调，以响应各种炎症/免疫介质，包括细胞应激。已知NF-κ B信号通路对于ICAM-1转录的激活是重要的。在这里，我们证明，ICAM-1诱导代表了一种新的细胞反应p53激活和NF-κ B抑制并不能阻止DNA损伤后的ICAM-1表达的p53的影响。ICAM-1的诱导在用特异性p53抑制剂pifithrin-alpha处理后被消除，并且在p53缺陷细胞系中被消除。此外，我们将两个功能性p53响应元件映射到ICAM-1基因的内含子，并显示它们以类似于其他p53靶基因的方式赋予p53诱导性。这些结果支持p53在ICAM-1调节中的NF-κ B非依赖性作用，其可能在各种生理和病理环境中将p53与ICAM-1功能联系起来。
Intercellular adhesion molecule-1 (ICAM-1) is a crucial receptor in the cell-cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a variety of inflammatory/immune mediators, including cellular stresses. The NF-kappaB signalling pathway is known to be important for activation of ICAM-1 transcription. Here we demonstrate that ICAM-1 induction represents a new cellular response to p53 activation and that NF-kappaB inhibition does not prevent the effect of p53 on ICAM-1 expression after DNA damage. Induction of ICAM-1 is abolished after treatment with the specific p53 inhibitor pifithrin-alpha and is abrogated in p53-deficient cell lines. Furthermore, we map two functional p53- responsive elements to the introns of the ICAM-1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF-kappaB-independent role for p53 in ICAM-1 regulation that may link p53 to ICAM-1 function in various physiological and pathological settings.