Document Detail

Overexpression of EVI1 interferes with cytokinesis and leads to accumulation of cells with supernumerary centrosomes in G0/1 phase.
MedLine Citation:
PMID:  22894935     Owner:  NLM     Status:  MEDLINE    
Ectopic viral integration site 1 (EVI1), a transcription factor frequently overexpressed in myeloid neoplasias, has been implicated in the generation of malignancy-associated centrosomal aberrations and chromosomal instability. Here, we sought to investigate the underlying cause of centrosome amplification in EVI1-overexpressing cells. We found that overexpression of EVI1-HA in U2OS cells induced supernumerary centrosomes, which were consistently associated with enlarged nuclei or binuclear cells. Live cell imaging experiments identified cytokinesis failure as the underlying cause of this phenotype. In accordance with previous reports, EVI1 overexpression induced a partial cell cycle arrest in G0/1 phase, accompanied by elevated cyclin D1 and p21 levels, reduced Cdk2 activity and activation of the p53 pathway. Supernumerary centrosomes predominantly occurred in resting cells, as identified by low levels of the proliferation marker Ki-67, leading to the conclusion that they result from tetraploidization after cytokinesis failure and are confined to G0/1-arrested tetraploid cells. Depletion of p53 using siRNA revealed that further polyploidization of these cells was inhibited by the p53-dependent tetraploidy checkpoint.
Kadin Karakaya; Friederike Herbst; Claudia Ball; Hanno Glimm; Alwin Krämer; Harald Löffler
Related Documents :
22465535 - Development and characterization of cell culture systems from puntius (tor) chelynoides...
22563055 - Cardiac-specific deletion of the microtubule-binding protein cenp-f causes dilated card...
8612555 - Immunocytochemical localization of stanniocalcin cells in the rat kidney.
16476735 - Systematic evaluation of transcellular activities of secretory phospholipases a2. high ...
23388635 - Branching process deconvolution algorithm reveals a detailed cell-cycle transcription p...
8484755 - Transplasma membrane redox system in hl-60 cells is modulated during tpa-induced differ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-18     Completed Date:  2013-02-06     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3492-503     Citation Subset:  IM    
Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg; Heidelberg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Cycle Checkpoints
Cell Line, Tumor
Cell Nucleus / metabolism
Cell Proliferation
Centrosome / metabolism*
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
DNA-Binding Proteins / metabolism*
Feedback, Physiological
G0 Phase*
G1 Phase*
Ki-67 Antigen / metabolism
Signal Transduction
Transcription Factors / metabolism*
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/CCND1 protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/Ki-67 Antigen; 0/MECOM protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 136601-57-5/Cyclin D1
Comment In:
Cell Cycle. 2012 Nov 1;11(21):3915   [PMID:  23032258 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Lithocholic acid extends longevity of chronologically aging yeast only if added at certain critical ...
Next Document:  Something in the Way She Sings: Enhanced Memory for Vocal Melodies.