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p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1

  • Oncogenomics
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Abstract

The mechanisms by which p53 prevents development of cancer are much more complicated than previously thought. Under normal conditions, p53 is involved in cell-cycle arrest, Q1apoptosis, DNA repair, and inhibition of angiogenesis; it also promotes degradation of proteins through transcriptional regulation of certain target genes. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21WAF1 protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21WAF1. p53RFP appears to represent the second known example, the first being MDM2, of an E3 ubiquitin ligase as a p53 target. Our results further suggest that p53 might regulate the stability of p21WAF1 through transcriptional regulation of p53RFP, and this feature may represent a novel mechanism for a p53-dependent cell-cycle checkpoint.

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Acknowledgements

We thank Dr Bert Vogelstein for HCT116 (p53+/+) and HCT116 (p53−/−) cell line and Dr K Miyazono for the HA-ubiquitin plasmid. We also thank K Matsui and S Onoue for their excellent technical assistance. This work was supported in part by Research for the Future Program Grant 00 L01402 from the Japan Society for the Promotion of Science (to YN), and in part by Grant 13216031 from the Ministry of Education, Culture, Sports, Science and Technology (to HA).

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Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Ching-Ching Ng, Hirofumi Arakawa, Seisuke Fukuda & Yusuke Nakamura

  2. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Ching-Ching Ng & Hisato Kondoh

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  1. Ching-Ching Ng
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  2. Hirofumi Arakawa
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  3. Seisuke Fukuda
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  4. Hisato Kondoh
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  5. Yusuke Nakamura
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Correspondence to Yusuke Nakamura.

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Ng, CC., Arakawa, H., Fukuda, S. et al. p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Oncogene 22, 4449–4458 (2003). https://doi.org/10.1038/sj.onc.1206586

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