作者
Qiang Wen, Benjamin Goldenson, Serena J Silver, Monica Schenone, Vlado Dancik, Zan Huang, Ling-Zhi Wang, Timothy A Lewis, W Frank An, Xiaoyu Li, Mark-Anthony Bray, Clarisse Thiollier, Lauren Diebold, Laure Gilles, Martha S Vokes, Christopher B Moore, Meghan Bliss-Moreau, Lynn VerPlank, Nicola J Tolliday, Rama Mishra, Sasidhar Vemula, Jianjian Shi, Lei Wei, Reuben Kapur, Cécile K Lopez, Bastien Gerby, Paola Ballerini, Francoise Pflumio, D Gary Gilliland, Liat Goldberg, Yehudit Birger, Shai Izraeli, Alan S Gamis, Franklin O Smith, William G Woods, Jeffrey Taub, Christina A Scherer, James E Bradner, Boon-Cher Goh, Thomas Mercher, Anne E Carpenter, Robert J Gould, Paul A Clemons, Steven A Carr, David E Root, Stuart L Schreiber, Andrew M Stern, John D Crispino
发表日期
2012/8/3
期刊
Cell
卷号
150
期号
3
页码范围
575-589
出版商
Elsevier
简介
The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and …
学术搜索中的文章
Q Wen, B Goldenson, SJ Silver, M Schenone, V Dancik… - Cell, 2012