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Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells

Oncogene volume 25, pages 6618–6627 (2006)Cite this article

An Erratum to this article was published on 16 November 2006

Abstract

Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated protein which is localized in either the cell membrane or nucleus depending on its palmitoylated state. The increasing evidence showed the biological roles of PLSCR1 in cell signaling, maturation and apoptosis. To investigate the functions of PLSCR1 in leukemic cells, we generated an inducible PLSCR1-expressing cell line using myeloid leukemic U937 cells. In this cell line, PLSCR1 was tightly regulated and induced upon tetracycline withdrawal. Our results showed that inducible PLSCR1 expression arrested the proliferation of U937 cells at G1 phase. Meanwhile, PLSCR1-overexpressing U937 cells also underwent granulocyte-like differentiation with increased sensitivity to etoposide-induced apoptosis. Furthermore, we also found that PLSCR1 induction increased cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 proteins, together with downregulation of S phase kinase-associated protein 2 (SKP2), an F-box subunit of the ubiquitin-ligase complex that targets proteins for degradation. Additionally, PLSCR1 induction significantly decreased c-Myc protein and antiapoptotic Bcl-2 protein. Although the exact mechanism by which PLSCR1 regulates these cellular events and gene expression remains unresolved, our results suggest that PLSCR1 plays the antagonistic role regarding leukemia development. These data will shed new insights into understanding the biochemical and biological functions of PLSCR1 protein.

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Acknowledgements

We thank Dr Tenen DG for providing us with U937T cells. We also deeply appreciate two anonymous reviewers for their thoughtful comments on this work. Miss Y Huang is a PhD candidate at Shanghai Institutes for Biological Sciences, and this work is submitted in partial fulfillment of the requirement for the PhD. This work was supported by grants from the National Key Program (973) for Basic Research of China (NO2002CB512806), Key Project for International Collaboration of Ministry of Science and Technology of China (2003DF000038), National Natural Science Foundation of China (90408009, 30470736) and grants from Science and Technology Commission of Shanghai (05JC14032, 03XD14016, 04QMX1467), and grants HL036946 and HL076215 from the National Institutes of Health of USA. Dr GQ Chen is a Chang Jiang Scholar of Ministry of Education of People's Republic of China, and is supported by Shanghai Ling-Jun Talent Program.

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  1. Y Huang and Q Zhao: These two authors equally contributed to this work.

Authors and Affiliations

  1. Institute of Health Science, Shanghai Institutes for Biological Sciences and Graduate School of Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM, formerly Shanghai Second Medical University), Shanghai, China

    Y Huang, Q Zhao, C-X Zhou, Z-M Gu & G-Q Chen

  2. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China

    D Li, H-Z Xu, K-W Zhao & G-Q Chen

  3. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

    P J Sims

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Huang, Y., Zhao, Q., Zhou, CX. et al. Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells. Oncogene 25, 6618–6627 (2006). https://doi.org/10.1038/sj.onc.1209677

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