IL-1 Induces Expression of p21WAF1 Independently of p53 in High-Passage Human Embryonic Fibroblasts WI38.

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Author(s)

    • Osawa Yoshiaki
    • Division of Radiation Health, National Institute of Radiological Sciences
    • Hachiya Misao
    • Division of Radiation Health, National Institute of Radiological Sciences
    • Araki Shun-ichi
    • Department of Public Health, Faculty of Medicine, The University of Tokyo
    • Matsushima Kouji
    • Department of Molecular Preventive Medicine, Faculty of Medicine, The University of Tokyo
    • Aoki Yoshiro
    • Nuclear Safety Commission, Science and Technology Agency
    • Akashi Makoto
    • Division of Radiation Health, National Institute of Radiological Sciences

Abstract

We tested the effect of IL-1 on the expression of p21<sup>WAF1</sup> in human embryonic fibroblasts W138. Exposure to IL-1 caused induction of p21<sup>WAF1</sup> protein in high-passage W138 cells but not in early-passage cells. However, IL-1 did not stimulate the transcription of a CAT-reporter gene having two copies of the p53-responsive element on its promoter or the p53-binding capacity of nuclear extracts, although it increased transcriptional rate of p21<sup>WAF1</sup> in these high-passage cells. These results suggest that the induction of p21<sup>WAF1</sup> by IL-1 occurs at the transcriptional level, but p53 function is not required in these cells. Further studies found that IL-1 did not cause cell-cycle arrest, and the overexpression of p21<sup>WAF1</sup> resulted in only a slight delay of cell growth, while the level of p21<sup>WAF1</sup> coprecipitated with cyclin-dependent kinase-2 (Cdk2) was increased by IL-1. Moreover, a kinase assay of Cdk2 immunoprecipitates showed that IL-1 did not reduce the kinase activity, and IL-1 did not affect the status of phosphorylation of the retinoblastoma gene product (Rb). These findings imply that despite the induction of p21<sup>WAF1</sup>, this cannot fully account for the growth arrest in high-passage W138 cells. Thus, IL-1 mediates p21<sup>WAF1</sup> induction through a p53-independent pathway (s) in high-passage W138 cells, but the cell cycle is regulated independently of p21<sup>WAF1</sup>.

Journal

  • J Biochem (Tokyo)

    J Biochem (Tokyo) 127(5), 883-893, 2000

    The Japanese Biochemical Society

Codes

  • NII Article ID (NAID)
    130003533879
  • Text Lang
    EN
  • ISSN
    0021-924X
  • Data Source
    J-STAGE 
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