Mourtada-Maarabouni Mirna, Keen Jennifer, Clark Jeremy, Cooper Colin S, Williams Gwyn T
School of Life Sciences, Keele University, Keele ST5 5BG, UK.
Exp Cell Res. 2006 Jun 10;312(10):1745-52. doi: 10.1016/j.yexcr.2006.02.009. Epub 2006 Mar 20.
RBM5 (RNA-binding motif protein 5/LUCA-15/H37) is encoded at the lung cancer tumor suppressor locus 3p21.3 and itself has several important characteristics of a tumor suppressor, including both potentiation of apoptosis and inhibition of the cell cycle. Here, we report the effects of both upregulation and downregulation of LUCA-15/RBM5 on gene expression monitored using cDNA microarrays. Many of the genes modulated by LUCA-15/RBM5 are involved in the control of apoptosis, the cell cycle, or both. These effects were confirmed for the most significant genes using real-time RT-PCR and/or Western blotting. In particular, LUCA-15/RBM5 increased the expression of Stat5b and BMP5 and decreased the expression of AIB1 (Amplified In Breast Cancer 1), proto-oncogene Pim-1, caspase antagonist BIRC3 (cIAP-2, MIHC), and CDK2 (cyclin-dependent kinase 2). These effects on multiple genes controlling both apoptosis and proliferation are in line with the functional effects of LUCA-15/RBM5 and indicate that it plays a central role in regulating cell fate consistent with its tumor suppressor activity.
RBM5（RNA结合基序蛋白5/LUCA-15/H37）由肺癌肿瘤抑制基因座3p21.3编码，自身具有多种肿瘤抑制的重要特征，包括增强细胞凋亡和抑制细胞周期。在此，我们报告了使用cDNA微阵列监测LUCA-15/RBM5上调和下调对基因表达的影响。许多受LUCA-15/RBM5调控的基因参与细胞凋亡、细胞周期或两者的调控。使用实时RT-PCR和/或蛋白质印迹法对最显著的基因进行了验证。特别是，LUCA-15/RBM5增加了Stat5b和BMP5的表达，并降低了AIB1（乳腺癌扩增基因1）、原癌基因Pim-1、半胱天冬酶拮抗剂BIRC3（细胞凋亡抑制蛋白2，MIHC）和CDK2（细胞周期蛋白依赖性激酶2）的表达。这些对控制细胞凋亡和增殖的多个基因的影响与LUCA-15/RBM5的功能作用一致，表明它在调节细胞命运中发挥核心作用，与其肿瘤抑制活性相符。
