A proinflammatory cytokine inhibits p53 tumor suppressor activity.

A proinflammatory cytokine inhibits p53 tumor suppressor activity.
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DOI:
10.1084/jem.190.10.1375
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发表时间:
1999-11-15
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Beach DH
Beach DH
中科院分区:
其他
文献类型:
--
作者:
Hudson JD;Shoaibi MA;Maestro R;Carnero A;Hannon GJ;Beach DH

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p53在细胞增殖的负调节、基因组稳定性的维持以及转化和肿瘤发生的抑制中具有关键作用。为了确定新的调节p53,我们进行了两个功能性筛选,以分离绕过p53介导的生长停滞或凋亡的基因。在这两种筛选中,我们分离出编码巨噬细胞移动抑制因子(MIF)的cDNA,MIF是一种细胞因子,以前被证明可以发挥局部和全身促炎活性。在三种不同的生物测定中,用MIF治疗克服了p53活性,并抑制了其作为转录激活因子的活性。促炎细胞因子MIF能够使肿瘤抑制因子p53功能性失活,这一观察结果可能提供了炎症和肿瘤发生之间的联系。
p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two functional screens to isolate genes which bypassed either p53-mediated growth arrest or apoptosis. In both screens, we isolated cDNAs encoding macrophage migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppressed its activity as a transcriptional activator. The observation that a proinflammatory cytokine, MIF, is capable of functionally inactivating a tumor suppressor, p53, may provide a link between inflammation and tumorigenesis.
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发表时间: 1996-10-01
影响因子: 4.1
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通讯作者: Brune, B
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