Blasi Francesco, Bruckmann Chiara, Penkov Dmitry, Dardaei Leila
IFOM, Foundation FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.
Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.
Bioessays. 2017 May;39(5). doi: 10.1002/bies.201600245. Epub 2017 Mar 21.
We report the latest structural information on PREP1 tumor suppressor, the specific "oncogene" and "tumor suppressive" signatures of MEIS1 and PREP1, the molecular rules regulating PREP1 and MEIS1 binding to DNA, and how these can change depending on the interaction with PBX1, cell-type, neoplastic transformation, and intracellular concentration. As both PREP1 and MEIS1 interact with PBX1 they functionally compete with each other. PREP1, PBX1, and MEIS1 TALE-class homeodomain transcription factors act in an interdependent and integrated way in experimental tumorigenesis. We also pool together the plethora of data available in human cancer databanks and connect them with the available molecular information. The emerging picture suggests that a similarly basic approach might be used to better dissect and define other oncogenes and suppressors and better understand human cancer.
我们报告了PREP1肿瘤抑制因子的最新结构信息、MEIS1和PREP1的特定“致癌基因”和“肿瘤抑制”特征、调节PREP1和MEIS1与DNA结合的分子规则，以及这些规则如何根据与PBX1的相互作用、细胞类型、肿瘤转化和细胞内浓度而变化。由于PREP1和MEIS1都与PBX1相互作用，它们在功能上相互竞争。PREP1、PBX1和MEIS1三结构域同源异型转录因子在实验性肿瘤发生中以相互依赖和整合的方式发挥作用。我们还汇总了人类癌症数据库中大量可用数据，并将它们与现有的分子信息联系起来。新出现的情况表明，可能会采用类似的基本方法来更好地剖析和定义其他致癌基因和抑制因子，并更好地理解人类癌症。
