Johnson Sandra S, Zhang Cheng, Fromm Jody, Willis Ian M, Johnson Deborah L
Department of Biochemistry and Molecular Biology, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Mol Cell. 2007 May 11;26(3):367-79. doi: 10.1016/j.molcel.2007.03.021.
Most eukaryotic transcriptional regulators act in an RNA polymerase (Pol)-selective manner. Here we show that the human Maf1 protein negatively regulates transcription by all three nuclear Pols. Changes in Maf1 expression affect Pol I- and Pol III-dependent transcription in human glioblastoma lines. These effects are mediated, in part, through the ability of Maf1 to repress transcription of the TATA binding protein, TBP. Maf1 targets an Elk-1-binding site in the TBP promoter, and its occupancy of this region is reciprocal with that of Elk-1. Similarly, Maf1 occupancy of Pol III genes is inversely correlated with that of the initiation factor TFIIIB and Pol III. The phenotypic consequences of reducing Maf1 expression include changes in cell morphology and the accumulation of actin stress fibers, whereas Maf1 overexpression suppresses anchorage-independent growth. Together with the ability of Maf1 to reduce biosynthetic capacity, these findings support the idea that Maf1 regulates the transformation state of cells.
大多数真核转录调节因子以RNA聚合酶（Pol）选择性方式发挥作用。在此我们表明，人类Maf1蛋白对所有三种核Pol的转录均起负调节作用。Maf1表达的变化影响人胶质母细胞瘤细胞系中依赖Pol I和Pol III的转录。这些效应部分是通过Maf1抑制TATA结合蛋白（TBP）转录的能力介导的。Maf1靶向TBP启动子中的一个Elk-1结合位点，其对该区域的占据情况与Elk-1相反。同样，Maf1对Pol III基因的占据与起始因子TFIIIB和Pol III的占据呈负相关。降低Maf1表达的表型后果包括细胞形态变化和肌动蛋白应激纤维的积累，而Maf1过表达则抑制非锚定依赖性生长。连同Maf1降低生物合成能力的能力，这些发现支持Maf1调节细胞转化状态这一观点。
