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Signal Transduction – Tumor Suppressor Genes and Cell Cycle

p21Cip1/WAF1 is important for differentiation and survival of U937 cells

Leukemia volume 12, pages 1944–1950 (1998)Cite this article

Abstract

Vitamin D3 (VD3) induces monocytic differentiation of U937 cells. Induction of p21Cip1/WAF1(p21) and subsequent G0/G1 cell-cycle arrest are required in this process. Using a system of inducible expression of ectopic p21, we demonstrated the important role of p21 in the induction of monocytic differentiation in U937 cells. Prior induction of antisense-p21 expression significantly suppressed p21 expression, and resulted in inhibition of VD3-induced U937 differentiation. Moreover, induction of expression of antisense-p21 in VD3-differentiated U937 cells resulted in apoptosis of the cells. This was associated with activation of Cdc2 and caspase-3 like protease. Our results suggest that p21 is required for the initiation of the early steps of differentiation as well as survival of differentiated cells.

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Author notes

  1. K Fukumuro

    Present address: Division of Hospital Pharmacy, Tokyo Women’s Medical College, 8-1 Kawado-cho, Shinjuku-ku, Tokyo, Japan

Authors and Affiliations

  1. Department of Virology, The National Children’s Medical Research Center, Tokyo, Japan

    M Asada, T Yamada & S Mizutani

  2. Department of Pharmacotherapeutics, Tokyo Science University, Tokyo, Japan

    K Fukumuro

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  1. M Asada
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  2. T Yamada
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  3. K Fukumuro
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  4. S Mizutani
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Asada, M., Yamada, T., Fukumuro, K. et al. p21Cip1/WAF1 is important for differentiation and survival of U937 cells. Leukemia 12, 1944–1950 (1998). https://doi.org/10.1038/sj.leu.2401228

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  • DOI: https://doi.org/10.1038/sj.leu.2401228

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