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  • Original Paper
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Nuclear exclusion of p53 in a subset of tumors requires MDM2 function

Oncogene volume 19, pages 232–240 (2000)Cite this article

Abstract

Wild type p53 accumulates in the cytoplasm in a subset of tumors such as neuroblastomas and breast carcinomas through an unknown mechanism. Exclusion of p53 from the nucleus may lead to inactivation of p53 during tumor development. We present evidence that MDM2 plays a significant role in promoting the degradation of nuclear p53 in tumor cells with a cytoplasmic p53 phenotype. Inhibition of MDM2 expression using antisense oligonucleotide, inhibition of MDM2 function by the tumor suppressor ARF or a MDM2 deletion mutant result in the accumulation of nuclear p53. p53 point mutants deficient in MDM2 binding have increased nuclear localization. Inhibition of nuclear export by leptomycin B also results in retention of nascent p53 in the nucleus, suggesting that cytoplasmic distribution of p53 results from efficient export of nuclear p53 in combination with MDM2-mediated degradation. These results suggest that MDM2 is an important determinant of p53 subcellular distribution and may contribute to p53 inactivation without overexpression.

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Acknowledgements

We thank Dr Yue Xiong for helpful discussions and providing reagents. We also thank Dr Jay Hunt for use of fluorescence microscope. This work is supported by a grant from the American Cancer Society to J Chen.

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Authors and Affiliations

  1. Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, 33612, Florida, FL, USA

    Wenge Lu, Radhika Pochampally, Lihong Chen, Yiliang Wang & Jiandong Chen

  2. Department of Microbiology, LSU Medical Center, 1901 Perdido Street, New Orleans, 70112, Louisiana, LA, USA

    Mullika Traidej

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  1. Wenge Lu
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Lu, W., Pochampally, R., Chen, L. et al. Nuclear exclusion of p53 in a subset of tumors requires MDM2 function. Oncogene 19, 232–240 (2000). https://doi.org/10.1038/sj.onc.1203262

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