Nguyen Hong, Mariotti Jolene, Bareyan Diana, Carnahan Robert, Cooper Tracy, Williams Christopher, Engel Michael
Department of Pediatrics, Vanderbilt University School of Medicine.
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine.
Antib Technol J. 2015;5:27-41. doi: 10.2147/anti.s74419. Epub 2015 Feb 19.
The myeloid translocation gene (MTG) family of transcriptional co-repressors consists of three highly conserved members; MTG8, MTG16 and MTGR1, each evolutionarily related to the protein NERVY and with orthologs across the mammalian hierarchy. By coordinating coincident interactions between DNA binding proteins, other co-repressors and epigenetic effectors, MTG proteins occupy a critical nexus in transcriptional control complexes to profoundly impact the specification of cell fate. MTG family members are most conserved within Nervy Homology Regions (NHR) 1-4, with each region fulfilling functions common to the family. Studies of functional differences between MTG proteins require carefully qualified immunologic reagents specific to each family member. We have developed a group of α-MTG16 antibodies and carefully characterized their specificity for MTG16. These tools reveal that MTG16 is concentrated in the cytoplasm of erythroleukemia cell lines from human and mouse. Using the CRM1 antagonist, leptomycin-B, we show that MTG16 levels rise in the nucleus of MEL cells and decline in the cytoplasm. Together, these data indicate bidirectional movement of MTG16 between cytoplasmic and nuclear compartments. Our work reveals an unrecognized feature of MTG16 regulation that may impact cell fate specification and provides reagents to address important questions regarding MTG16 functions .
转录共抑制因子的髓系易位基因（MTG）家族由三个高度保守的成员组成；MTG8、MTG16和MTGR1，它们在进化上与NERVY蛋白相关，并且在整个哺乳动物体系中有直系同源物。通过协调DNA结合蛋白、其他共抑制因子和表观遗传效应物之间的同步相互作用，MTG蛋白在转录控制复合物中占据关键节点，从而深刻影响细胞命运的决定。MTG家族成员在Nervy同源区域（NHR）1-4中最为保守，每个区域都履行着该家族共有的功能。对MTG蛋白之间功能差异的研究需要针对每个家族成员的经过严格鉴定的免疫试剂。我们已经开发了一组α-MTG16抗体，并仔细鉴定了它们对MTG16的特异性。这些工具显示MTG16集中在人和小鼠红白血病细胞系的细胞质中。使用CRM1拮抗剂 leptomycin-B，我们发现MTG16在MEL细胞的细胞核中水平升高，而在细胞质中水平下降。这些数据共同表明MTG16在细胞质和细胞核区室之间的双向移动。我们的工作揭示了MTG16调控的一个未被认识的特征，这可能影响细胞命运的决定，并提供试剂来解决有关MTG16功能的重要问题。
