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The c-Myc target glycoprotein1bα links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells

Saunders, WS and Wu, Q and Xu, FL and Li, Y and Prochownik, EV (2010) The c-Myc target glycoprotein1bα links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells. PLoS ONE, 5 (5).

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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 (GpIbα), a component of the c-Myc signaling pathway. We are able to recapitulate cytokinesis failure in primary cells by overexpression of GpIbα in a p53-deficient background. GpIbα was found to localize to the cleavage furrow by microscopy analysis and, when overexpressed, to interfere with assembly of the cellular cortical contraction apparatus and normal division. These results indicate that cytokinesis failure and tetraploidy in cancer cells are directly linked to cellular hyperproliferation via c-Myc induced overexpression of GpIbα.© 2010 Wu et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Saunders, WSwsaund@pitt.eduWSAUND
Wu, Q
Xu, FL
Li, Y
Prochownik, EVevp4@pitt.eduEVP4
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBlagosklonny, Mikhail V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 17 September 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0010819
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
MeSH Headings: Actins--metabolism; Animals; Cell Transformation, Neoplastic; Cells, Cultured; Contractile Proteins--metabolism; Cytokinesis; Gene Knockdown Techniques; Humans; Membrane Glycoproteins--chemistry; Membrane Glycoproteins--metabolism; Mice; Microfilament Proteins--metabolism; Myosin Heavy Chains--metabolism; Neoplasms--metabolism; Neoplasms--pathology; Phenotype; Protein Sorting Signals; Protein Structure, Tertiary; Protein Transport; Proto-Oncogene Proteins c-myc--metabolism; RNA, Small Interfering--metabolism; Signal Transduction; rhoA GTP-Binding Protein--metabolism
Other ID: NLM PMC2876040
PubMed Central ID: PMC2876040
PubMed ID: 20520840
Date Deposited: 03 Aug 2012 20:53
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/13366

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