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J. Biol. Chem., Vol. 276, Issue 46, 43413-43418, November 16, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/46/43413    most recent M106006200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ballester, A. Articles by Calés, C. Search for Related Content PubMed PubMed Citation Articles by Ballester, A. Articles by Calés, C. Social Bookmarking                      What's this?

Heterologous Expression of the Transcriptional Regulator Escargot Inhibits Megakaryocytic Endomitosis^*

Alicia Ballester, Jonathan Frampton^§, Nuria Vilaboa^¶, and Carmela Calés

From the  Department of Biochemistry, Instituto de Investigaciones Biomédicas "Alberto Sols," Universidad Autónoma-Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid, Spain and the ^§ Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom

Certain cell types escape the strict mechanisms imposed on the majority of somatic cells to ensure the faithful inheritance of parental DNA content. This is the case in many embryonic tissues and certain adult cells such as mammalian hepatocytes and megakaryocytes. Megakaryocytic endomitosis is characterized by repeated S phases followed by abortive mitoses, resulting in mononucleated polyploid cells. Several cell cycle regulators have been proposed to play an active role in megakaryocytic polyploidization; however, little is known about upstream factors that could control endomitosis. Here we show that ectopic expression of the transcriptional repressor escargot interferes with the establishment of megakaryocytic endomitosis. Phorbol ester-induced polyploidization was inhibited in stably transfected megakaryoblastic HEL cells constitutively expressing escargot. Analysis of the expression and activity of different cell cycle factors revealed that Escargot affects the G₁/S transition by influencing Cdk2 activity and cyclin A transcription. Nuclear proteins that specifically bind the Escargot-binding element were detected in endomitotic and non-endomitotic megakaryoblastic cells, but down-regulation occurred only during differentiation of cells that become polyploid. As Escargot was originally implicated in ploidy maintenance of Drosophila embryonic and larval cells, our results suggest that polyploidization in megakaryocytes might respond to mechanisms conserved from early development to adult cells that need to escape normal control of the diploid state.

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