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Proteomic analysis of acute promyelocytic leukemia: PML-RARα leads to decreased phosphorylation of OP18 at serine 63

2006; Wiley; Volume: 6; Issue: 21 Linguagem: Inglês

10.1002/pmic.200600307

1615-9861

Abdul Ali Peer‐Zada, M. Geletu, John Anto Pulikkan, Carsten Müller‐Tidow, Venkateshwar A. Reddy, Maximilian Christopeit, Wolfgang Hiddemann, Hermann M. Behre, Daniel G. Tenen, Gerhard Behre,

Acute Myeloid Leukemia Research

PROTEOMICSVolume 6, Issue 21 p. 5705-5719 Systems Biology Proteomic analysis of acute promyelocytic leukemia: PML-RARα leads to decreased phosphorylation of OP18 at serine 63 Abdul A. Peer Zada, Abdul A. Peer Zada BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorMulu H. Geletu, Mulu H. Geletu BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorJohn A. Pulikkan, John A. Pulikkan BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorCarsten Müller-Tidow, Carsten Müller-Tidow Medizinische Klinik A, Universitätsklinikum Münster, Münster, GermanySearch for more papers by this authorVenkateshwar A. Reddy, Venkateshwar A. Reddy BMT Unit, Internal Medicine IV, MLU University, Halle, GermanySearch for more papers by this authorMaximilian Christopeit, Maximilian Christopeit BMT Unit, Internal Medicine IV, MLU University, Halle, GermanySearch for more papers by this authorWolfgang D. Hiddemann, Wolfgang D. Hiddemann Department of Medicine III, University Hospital Grosshadern, Munich, GermanySearch for more papers by this authorHermann M. Behre, Hermann M. Behre Andrology Section, MLU University, Halle, GermanySearch for more papers by this authorDaniel G. Tenen, Daniel G. Tenen Harvard Institutes of Medicine, Boston, MA, USASearch for more papers by this authorGerhard Behre Dr., Corresponding Author Gerhard Behre Dr. gerhard.behre@medizin.uni-halle.de BMT Unit, Internal Medicine IV, MLU University, Halle, GermanyBMT Unit, Internal Medicine IV, MLU University, Halle, Germany Fax: +49-345-5577279===Search for more papers by this author Abdul A. Peer Zada, Abdul A. Peer Zada BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorMulu H. Geletu, Mulu H. Geletu BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorJohn A. Pulikkan, John A. Pulikkan BMT Unit, Internal Medicine IV, MLU University, Halle, Germany These authors contributed equally to this work.Search for more papers by this authorCarsten Müller-Tidow, Carsten Müller-Tidow Medizinische Klinik A, Universitätsklinikum Münster, Münster, GermanySearch for more papers by this authorVenkateshwar A. Reddy, Venkateshwar A. Reddy BMT Unit, Internal Medicine IV, MLU University, Halle, GermanySearch for more papers by this authorMaximilian Christopeit, Maximilian Christopeit BMT Unit, Internal Medicine IV, MLU University, Halle, GermanySearch for more papers by this authorWolfgang D. Hiddemann, Wolfgang D. Hiddemann Department of Medicine III, University Hospital Grosshadern, Munich, GermanySearch for more papers by this authorHermann M. Behre, Hermann M. Behre Andrology Section, MLU University, Halle, GermanySearch for more papers by this authorDaniel G. Tenen, Daniel G. Tenen Harvard Institutes of Medicine, Boston, MA, USASearch for more papers by this authorGerhard Behre Dr., Corresponding Author Gerhard Behre Dr. gerhard.behre@medizin.uni-halle.de BMT Unit, Internal Medicine IV, MLU University, Halle, GermanyBMT Unit, Internal Medicine IV, MLU University, Halle, Germany Fax: +49-345-5577279===Search for more papers by this author First published: 26 October 2006 https://doi.org/10.1002/pmic.200600307Citations: 10 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract In the present study, we employed 2-DE to characterize the effect of the acute promyelocytic leukemia (APL)-specific PML-RARα fusion protein on the proteome. Differentially expressed proteins, a number of which are related to the cell cycle function, including oncoprotein18 (OP18), heat shock protein70, glucose-regulated protein75, and peptidyl-prolyl isomerase, were identified by MS. Subsequent bioinformatic pathway discovery revealed an integrated network constituting SMARCB1, MYC, and TP53-regulated pathways. The data from the DNA microarray and proteomic experiments demonstrated the correlation between the translocation and higher expression of OP18 at mRNA and protein levels. Transient cotransfection assay revealed that PML-RARα is a potent activator of OP18 promoter and this transcriptional activation is retinoic acid sensitive. PML-RARα induction also leads to decreased phosphorylation on Ser63 residue of OP18, which is okadaic acid sensitive suggesting the involvement of a phosphatase pathway. Overexpression of a constitutively phosphorylated Ser63 mutant of OP18 in PML-RARα expressing APL patient, PR9, and NB4 cells led to a G2/M-phase arrest in contrast to a phosphorylation-deficient Ser63 mutant and untransfected control. Taken together, our results demonstrate the significance of decreased Ser63 phosphorylation of OP18 in PML-RARα-mediated effects on cell cycle. Citing Literature Supporting Information Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2120/2006/pro200600307_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume6, Issue21No. 21 November 2006Pages 5705-5719 RelatedInformation