Document Detail


New roles for cyclin E in megakaryocytic polyploidization.
MedLine Citation:
PMID:  20392692     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Megakaryocytes are platelet precursor cells that undergo endomitosis. During this process, repeated rounds of DNA synthesis are characterized by lack of late anaphase and cytokinesis. Physiologically, the majority of the polyploid megakaryocytes in the bone marrow are cell cycle arrested. As previously reported, cyclin E is essential for megakaryocyte polyploidy; however, it has remained unclear whether up-regulated cyclin E is an inducer of polyploidy in vivo. We found that cyclin E is up-regulated upon stimulation of primary megakaryocytes by thrombopoietin. Transgenic mice in which elevated cyclin E expression is targeted to megakaryocytes display an increased ploidy profile. Examination of S phase markers, specifically proliferating cell nuclear antigen, cyclin A, and 5-bromo-2-deoxyuridine reveals that cyclin E promotes progression to S phase and cell cycling. Interestingly, analysis of Cdc6 and Mcm2 indicates that cyclin E mediates its effect by promoting the expression of components of the pre-replication complex. Furthermore, we show that up-regulated cyclin E results in the up-regulation of cyclin B1 levels, suggesting an additional mechanism of cyclin E-mediated ploidy increase. These findings define a key role for cyclin E in promoting megakaryocyte entry into S phase and hence, increase in the number of cell cycling cells and in augmenting polyploidization.
Authors:
Alexia Eliades; Nikolaos Papadantonakis; Katya Ravid
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-06-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18909-17     Citation Subset:  IM    
Affiliation:
Department of Medicine and Biochemistry, Evans Center for Interdisciplinary Biomedical Research, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Platelets / metabolism
Bone Marrow / metabolism
Cyclin B1 / metabolism
Cyclin E / chemistry*
Cyclins / metabolism
DNA / chemistry*
Deoxyuridine / analogs & derivatives,  metabolism
Gene Expression Regulation*
Megakaryocytes / metabolism*
Mice
Mice, Transgenic
Polyploidy
S Phase
Thrombopoietin / metabolism
Grant Support
ID/Acronym/Agency:
HL80442/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin B1; 0/Cyclin E; 0/Cyclins; 80384-36-7/5-bromoethynyl-2'-deoxyuridine; 9007-49-2/DNA; 9014-42-0/Thrombopoietin; 951-78-0/Deoxyuridine
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