Winner Millicent, Leng Lin, Zundel Wayne, Mitchell Robert A
Molecular Targets Program, JG Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Methods Enzymol. 2007;435:355-69. doi: 10.1016/S0076-6879(07)35018-0.
Increasingly clear is an important regulatory role for hypoxia-inducible factor 1alpha (HIF-1alpha) in the expression of the cytokine/growth factor macrophage migration inhibitory factor (MIF). The functional significance of hypoxia-induced MIF expression is revealed by findings demonstrating that HIF-1alpha-dependent MIF expression is necessary for hypoxia-induced evasion from cell senescence and that MIF is necessary for HIF-1alpha stabilization induced by hypoxia and prolyl hydroxylase (PHD) inhibitors. Both of these activities attributed to MIF likely involve the modulation of protein degratory pathways mediated by cullin-dependent E3 ubiquitin ligase complexes and their regulation by the COP9 signalosome (CSN). As the importance of MIF in hypoxic adaptation of human tumors is now becoming fully realized, we review protocols designed to evaluate MIF expression, activity, and functional consequences in hypoxic environments.
缺氧诱导因子1α（HIF-1α）在细胞因子/生长因子巨噬细胞移动抑制因子（MIF）的表达中发挥重要调节作用，这一点越来越清晰。缺氧诱导MIF表达的功能意义通过以下研究结果得以揭示：表明缺氧诱导的逃避细胞衰老需要HIF-1α依赖的MIF表达，并且MIF对于缺氧和脯氨酰羟化酶（PHD）抑制剂诱导的HIF-1α稳定是必需的。归因于MIF的这两种活性可能都涉及由cullin依赖性E3泛素连接酶复合物介导的蛋白质降解途径的调节及其受COP9信号体（CSN）的调控。由于MIF在人类肿瘤缺氧适应中的重要性现在已得到充分认识，我们综述了旨在评估缺氧环境中MIF表达、活性和功能后果的方案。
