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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3731-3738. Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-04-1630. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1630v1 104/12/3731    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhao, K.-W. Articles by Chen, G.-Q. Search for Related Content PubMed PubMed Citation Articles by Zhao, K.-W. Articles by Chen, G.-Q. Related Collections Signal Transduction Gene Expression Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Protein kinase C mediates retinoic acid and phorbol myristate acetate–induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation Ke-Wen Zhao, Xi Li, Qian Zhao, Ying Huang, Dong Li, Zhen-Gang Peng, Wu-Zhong Shen, Ji Zhao, Quansheng Zhou, Zhu Chen, Peter J. Sims, Therese Wiedmer, and Guo-Qiang Chen From the Health Science Center, Shanghai Second Medical University (SSMU)–Shanghai Institutes for Biological Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China; the Department of Pathophysiology, Shanghai Terry Fox Cancer Center and Institute of Hematology, Rui-Jin Hospital, SSMU, Shanghai, China; and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA. Although phospholipid scramblase 1 (PLSCR1) was originally identified based on its capacity to promote transbilayer movement of membrane phospholipids, subsequent studies also provided evidence for its role in cell proliferation, maturation, and apoptosis. In this report, we investigate the potential role of PLSCR1 in leukemic cell differentiation. We show that all-trans retinoic acid (ATRA), an effective differentiation-inducing agent of acute promyelocytic leukemic (APL) cells, can elevate PLSCR1 expression in ATRA-sensitive APL cells NB4 and HL60, but not in maturation-resistant NB4-LR1 cells. ATRA- and phorbol 12-myristate 13-acetate (PMA)–induced monocytic differentiation is accompanied by increased PLSCR1 expression, whereas only a slight or no elevation of PLSCR1 expression is observed in U937 cells differentiated with dimethyl sulfoxide (DMSO), sodium butyrate, or vitamin D3. Cell differentiation with ATRA and PMA, but not with vitamin D3 or DMSO, results in phosphorylation of protein kinase C (PKC), and the PKC-specific inhibitor rottlerin nearly eliminates the ATRA- and PMA-induced expression of PLSCR1, while ectopic expression of a constitutively active form of PKC directly increases PLSCR1 expression. Finally, decreasing PLSCR1 expression with small interfering RNA inhibits ATRA/PMA-induced differentiation. Taken together, these results suggest that as a protein induced upon PKC activation, PLSCR1 is required for ATRA- and PMA-triggered leukemic cell differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Moserle, S. Indraccolo, M. Ghisi, C. Frasson, E. Fortunato, S. Canevari, S. Miotti, V. Tosello, R. Zamarchi, A. Corradin, et al. The Side Population of Ovarian Cancer Cells Is a Primary Target of IFN-{alpha} Antitumor Effects Cancer Res., July 15, 2008; 68(14): 5658 - 5668. [Abstract] [Full Text] [PDF] D. Smrz, P. Lebduska, L. Draberova, J. Korb, and P. Draber Engagement of Phospholipid Scramblase 1 in Activated Cells: IMPLICATION FOR PHOSPHATIDYLSERINE EXTERNALIZATION AND EXOCYTOSIS J. Biol. Chem., April 18, 2008; 283(16): 10904 - 10918. [Abstract] [Full Text] [PDF] L. Yang, Y. Jiang, S.F. Wu, M.Y. Zhou, Y.L. Wu, and G.Q. Chen CCAAT/enhancer-binding protein {alpha} antagonizes transcriptional activity of hypoxia-inducible factor 1 {alpha} with direct protein-protein interaction Carcinogenesis, February 1, 2008; 29(2): 291 - 298. [Abstract] [Full Text] [PDF] L. Brizuela, M. Rabano, A. Pena, P. Gangoiti, J. M. Macarulla, M. Trueba, and A. Gomez-Munoz Sphingosine 1-phosphate: a novel stimulator of aldosterone secretion J. Lipid Res., June 1, 2006; 47(6): 1238 - 1249. [Abstract] [Full Text] [PDF] W. Liu, M. Guo, Y.-B. Xu, D. Li, Z.-N. Zhou, Y.-L. Wu, Z. Chen, S. C. Kogan, and G.-Q. Chen Induction of tumor arrest and differentiation with prolonged survival by intermittent hypoxia in a mouse model of acute myeloid leukemia Blood, January 15, 2006; 107(2): 698 - 707. [Abstract] [Full Text] [PDF] K.-W. Zhao, D. Li, Q. Zhao, Y. Huang, R. H. Silverman, P. J. Sims, and G.-Q. Chen Interferon-{alpha}-induced Expression of Phospholipid Scramblase 1 through STAT1 Requires the Sequential Activation of Protein Kinase C{delta} and JNK J. Biol. Chem., December 30, 2005; 280(52): 42707 - 42714. [Abstract] [Full Text] [PDF] Q. Zhou, I. Ben-Efraim, J.-L. Bigcas, D. Junqueira, T. Wiedmer, and P. J. Sims Phospholipid Scramblase 1 Binds to the Promoter Region of the Inositol 1,4,5-Triphosphate Receptor Type 1 Gene to Enhance Its Expression J. Biol. Chem., October 14, 2005; 280(41): 35062 - 35068. [Abstract] [Full Text] [PDF] Y. Z. Xu, S. Di Marco, I. Gallouzi, M. Rola-Pleszczynski, and D. 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