IL-1 Induces Expression of p21WAF1 Independently of p53 in High-Passage Human Embryonic Fibroblasts WI38.
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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>.
- J Biochem (Tokyo)
J Biochem (Tokyo) 127(5), 883-893, 2000
The Japanese Biochemical Society