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

p21Cip1/WAF1 is important for differentiation and survival of U937 cells
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DOI:
10.1038/sj.leu.2401228
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发表时间:
1998-12-01
期刊:
影响因子:
11.4
通讯作者:
Mizutani, S
Mizutani, S
中科院分区:
医学1区
文献类型:
--
作者:
Asada, M;Yamada, T;Mizutani, S

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维生素D3(VD 3)诱导U937细胞的单核细胞分化。在此过程中需要诱导p21 Cip 1/WAF 1(p21)和随后的G 0/G1细胞周期停滞。利用异位p21诱导表达系统,我们证明了p21在诱导U937细胞单核细胞分化中的重要作用。反义pal表达的预先诱导显著抑制pal表达,并导致VD 3诱导的U937分化的抑制。此外,在VD 3分化的U937细胞中诱导反义p21的表达导致细胞凋亡。这与Cdc 2和caspase-3样蛋白酶的激活有关。我们的研究结果表明,p21是所需的分化的早期步骤的启动以及分化细胞的存活。
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-pal expression significantly suppressed pal 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.