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Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1

Oncogene volume 20, pages 2134–2143 (2001)Cite this article

Abstract

A recently discovered potential tumor suppressor protein, Zac1, was previously shown to promote cell cycle arrest and apoptosis, and to act as a positive or negative transcriptional cofactor for nuclear receptors. Since these activities are common to Zac1 and p53, we tested for a functional interaction between these two proteins by investigating possible effects of Zac1 on the transcriptional activator function of p53. Zac1 specifically enhanced the activity of p53-responsive promoters in cells expressing wild type p53. The same promoters were not activated by Zac1 in cells lacking functional p53, but the Zac1 effect was restored by co-expression of p53. Zac1 bound to p53 and enhanced the activity of p53 or its N-terminal transcriptional activation domain fused to the DNA binding domain of Gal4. These results indicate that Zac1 served as a transcriptional coactivator for p53. The enhancement of p53 activity by Zac1 was much more dramatic in HeLa cells than in other cell lines tested. HeLa cells express human papillomavirus type 18 E6 protein which inactivates and causes the degradation of p53. Physical and functional interactions observed between Zac1 and E6 protein indicated that the dramatic activity of Zac1 in HeLa cells was due not only to Zac1's coactivator effect on p53, but also to the ability of Zac1 to reverse E6 inhibition of p53.

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Acknowledgements

We thank Dr W El-Deiry (University of Pennsylvania) for providing plasmids used in this study. This work was supported by US Public Health Service grants DK55274 to MR Stallcup and CA74278 to AH Schönthal from the National Institutes of Health. S-M Huang was supported by a predoctoral fellowship from the Defense Department, Taiwan, Republic of China.

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  1. Shih-Ming Huang

    Present address: Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, Republic of China

Authors and Affiliations

  1. Department of Pathology, University of Southern California, Los Angeles, 90089, California, CA, USA

    Shih-Ming Huang & Michael R Stallcup

  2. Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, 90089, California, CA, USA

    Shih-Ming Huang & Michael R Stallcup

  3. Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, 90089, California, CA, USA

    Axel H Schönthal

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Huang, SM., Schönthal, A. & Stallcup, M. Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1. Oncogene 20, 2134–2143 (2001). https://doi.org/10.1038/sj.onc.1204298

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