Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.
Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.
复制标题
巨噬细胞迁移抑制因子以p53依赖性方式激活缺氧诱导因子。
DOI：
10.1371/journal.pone.0002215
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发表时间：
2008-05-21
期刊：
影响因子：
3.7
通讯作者：
Hirota, Kiichi
中科院分区：
文献类型：
--
作者：
Oda, Seiko;Oda, Tomoyuki;Nishi, Kenichiro;Takabuchi, Satoshi;Wakamatsu, Takuhiko;Tanaka, Tomoharu;Adachi, Takehiko;Fukuda, Kazuhiko;Semenza, Gregg L.;Hirota, Kiichi
巨噬细胞移动抑制因子（macrophage migration inhibitor factor，MIF）不仅是一种在多种炎症反应中起关键作用的细胞因子，而且还具有内分泌和酶促作用。MIF被鉴定为细胞内信号分子，并且与肿瘤进展过程有关，并且还强烈地增强新血管形成。已在多种器官的肿瘤中观察到MIF的过表达。MIF是低氧诱导的基因之一，具有低氧诱导因子1（HIF-1）依赖性。在人乳腺癌MCF-7和MDA-MB-231细胞以及骨肉瘤Saos-2细胞中研究了MIF对HIF-1活性的影响。我们证明，在MCF-7细胞中，在缺氧条件下，MIF的细胞内过表达或细胞外给药增强HIF-1的活化。突变分析的MIF和敲低的53表明，激活是不依赖于氧化还原活性的MIF，但对野生型p53。我们还表明，MIF受体CD 74参与HIF-1的活化，至少当MIF是在细胞外。MIF以p53依赖性方式调节HIF-1活性。除了MIF对免疫系统的有效作用之外，MIF还与赋予细胞增殖、细胞存活、血管生成和肿瘤侵袭性的基本过程相关。MIF和HIF-1α蛋白稳定性和反式激活活性之间的这种功能相互依赖性为MIF促进肿瘤发生提供了分子机制。
Macrophage migration inhibitory factor (MIF) is not only a cytokine which has a critical role in several inflammatory conditions but also has endocrine and enzymatic functions. MIF is identified as an intracellular signaling molecule and is implicated in the process of tumor progression, and also strongly enhances neovascularization. Overexpression of MIF has been observed in tumors from various organs. MIF is one of the genes induced by hypoxia in an hypoxia-inducible factor 1 (HIF-1)-dependent manner. The effect of MIF on HIF-1 activity was investigated in human breast cancer MCF-7 and MDA-MB-231 cells, and osteosarcoma Saos-2 cells. We demonstrate that intracellular overexpression or extracellular administration of MIF enhances activation of HIF-1 under hypoxic conditions in MCF-7 cells. Mutagenesis analysis of MIF and knockdown of 53 demonstrates that the activation is not dependent on redox activity of MIF but on wild-type p53. We also indicate that the MIF receptor CD74 is involved in HIF-1 activation by MIF at least when MIF is administrated extracellularly. MIF regulates HIF-1 activity in a p53-dependent manner. In addition to MIF's potent effects on the immune system, MIF is linked to fundamental processes conferring cell proliferation, cell survival, angiogenesis, and tumor invasiveness. This functional interdependence between MIF and HIF-1α protein stabilization and transactivation activity provide a molecular mechanism for promotion of tumorigenesis by MIF.
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影响因子：
11.4
作者：
Ema, M;Hirota, K;Fujii-Kuriyama, Y
通讯作者：
Fujii-Kuriyama, Y
DOI：
10.1084/jem.190.10.1375
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hudson JD;Shoaibi MA;Maestro R;Carnero A;Hannon GJ;Beach DH
通讯作者：
Beach DH
影响因子：
10.5
作者：
Bemis, L;Chan, DA;Zundel, W
通讯作者：
Zundel, W
影响因子：
32.4
作者：
Bucala, Richard;Donnelly, Seamas C.
通讯作者：
Donnelly, Seamas C.
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ