BRCA1 physically associates with p53 and stimulates its transcriptional activity (original) (raw)

Oncogene volume 16, pages 1713–1721 (1998)Cite this article

Abstract

Mutations of the BRCA1 tumor suppressor gene are the most commonly detected alterations in familial breast and ovarian cancer. Although BRCA1 is required for normal mouse development, the molecular basis for its tumor suppressive function remains poorly understood. We show here that BRCA1 increases p53-dependent transcription from the p21 WAF1/CIP1 and bax promoters. We also show that BRCA1 and p53 proteins interact both in vitro and in vivo. The interacting regions map, in vitro, to aa 224–500 of BRCA1 and the C-terminal domain of p53. Tumor-derived transactivation-deficient BRCA1 mutants are defective in co-activation of **p53**-dependent transcription and a truncation mutant of BRCA1 that retains the p53-interacting region acts as a dominant inhibitor of **p53**-dependent transcription. BRCA1 and p53 cooperatively induce apoptosis of cancer cells. The results indicate that BRCA1 and p53 may coordinately regulate gene expression in their role as tumor suppressors.

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Author notes

  1. Hongbing Zhang and Kumaravel Somasundaram: H Zhang and K Somasundaram contributed equally to this study

Authors and Affiliations

  1. Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Kumaravel Somasundaram, Hui Tian & Wafik S El-Deiry
  2. Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Kumaravel Somasundaram, Hui Tian & Wafik S El-Deiry
  3. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Hongbing Zhang, Kumaravel Somasundaram, Yi Peng, Hui Tian, Hongxiang Zhang, Daike Bi, Barbara L Weber & Wafik S El-Deiry
  4. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Barbara L Weber & Wafik S El-Deiry
  5. Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Barbara L Weber & Wafik S El-Deiry

Authors

  1. Hongbing Zhang
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  2. Kumaravel Somasundaram
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  3. Yi Peng
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  4. Hui Tian
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  5. Hongxiang Zhang
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  6. Daike Bi
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  7. Barbara L Weber
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  8. Wafik S El-Deiry
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Zhang, H., Somasundaram, K., Peng, Y. et al. BRCA1 physically associates with p53 and stimulates its transcriptional activity.Oncogene 16, 1713–1721 (1998). https://doi.org/10.1038/sj.onc.1201932

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