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P130 and its truncated form mediate p53-induced cell cycle arrest inRb−/− Saos2 cells

Oncogene volume 21, pages 7569–7579 (2002)Cite this article

Abstract

In the present study, we investigate the mechanism of how p53 induces growth arrest in Rb-defective Saos2 cells that express temperature-sensitive mutant p53 (ts p53). The activation of p53 at a permissive temperature (32.5°C) induces the cell cycle arrest at both the G1 and G2 stages. The induction of several p53-responsive genes as well as a small form of p130 (S-p130) was detected upon p53 activation. S-p130 retained the functions as a pocket protein and was dominant over p130 at the protein level after 36 h at 32.5°C. A canonical p53 binding site was identified in intron 4 of p130. Furthermore, a novel p53-inducible transcript containing a partial intron 4 sequence downstream of the p53 binding site and exon 5 of p130 was detected by RT–PCR, suggesting S-p130 is induced by p53 at transcriptional level. The results from gel shift assay and immunoprecipitation showed that S-p130 as well as p130 formed complexes with both E2F1 and E2F4 at a permissive temperature. Moreover, the transient expression of E1A (12S) and E2F1 effectively abrogated p53-induced cell cycle arrest. These results strongly suggested that p130 and its truncated form might substitute Rb in mediating p53-induced cell cycle arrest in Rb−/− Saos2 cells.

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Acknowledgements

This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. We thank Dr Chun Zhang for her excellent discussion.

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  1. Shuo Ren and Jingfei Wang: Shuo Ren and Jingfei Wang contributed equally to this study

Authors and Affiliations

  1. Department of Molecular Cellular Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan

    Chong-Feng Gao, Shuo Ren, Jingfei Wang, Sheng-Liang Zhang, Feng Jin, Takuma Nakajima & Nobuo Tsuchida

  2. Department of Molecular Craniofacial Embryology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Tokyo, 113-8549, Japan

    Masaaki Ikeda

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  1. Chong-Feng Gao
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Correspondence to Nobuo Tsuchida.

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Gao, CF., Ren, S., Wang, J. et al. P130 and its truncated form mediate p53-induced cell cycle arrest inRb−/− Saos2 cells. Oncogene 21, 7569–7579 (2002). https://doi.org/10.1038/sj.onc.1205933

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