the c-myc target glycoprotein1bα links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells原癌基因的目标glycoprotein1bα链接胞质分裂失败在培养的人类细胞致癌信号转导途径.pdf

The c-Myc Target Glycoprotein1ba Links Cytokinesis Failure to Oncogenic Signal Transduction Pathways in Cultured Human Cells 1.¤ 1. 2 2,3,4 1,4 Qian Wu , Fengfeng L. Xu , Youjun Li , Edward V. Prochownik , William S. Saunders * 1 Department of Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2 Section of Hematology/Oncology, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Department of Microbiology and Molecular Genetics, The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America, 4 University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America Abstract An increase in chromosome number, or polyploidization, is associated with a variety of biological changes including breeding of cereal crops and flowers, terminal differentiation of specialized cells such as megakaryocytes, cellular stress and oncogenic transformation. Yet it remains unclear how cells tolerate the major changes in gene expression, chromatin organization and chromosome segregation that invariably accompany polyploidization. We show here that cancer cells can initiate increases in chromosome number by inhibiting cell division through activation of glycoprotein1b alpha (GpIba), a component of the c-Myc signaling pathway. We are able to recapitulate cytokinesis failure in primary cells by overexpression of GpIba in a p53-deficient background. GpIba was found to localize to the cleavage furrow by microscopy analysis and, when overexpressed, to interfere with assembly of the cellular cortical c