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The function of PML in p53-dependent apoptosis

Nature Cell Biology volume 2, pages 730–736 (2000)Cite this article

Abstract

The PML gene of acute promyelocytic leukaemia (APL) encodes a growth- and tumour-suppresor protein that is essential for several apoptotic signals. The mechanisms by which PML exerts its pro-apoptotic function are still unknown. Here we show that PML acts as a transcriptional co-activator with p53. PML physically interacts with p53 both in vitro and in vivo and co-localizes with p53 in the PML nuclear body (PML-NB). The co-activatory role of PML depends on its ability to localize in the PML-NB. p53-dependent, DNA-damage-induced apoptosis, transcriptional activation by p53, the DNA-binding ability of p53, and the induction of p53 target genes such as Bax and p21 upon γ-irradiation are all impaired in PML−/− primary cells. These results define a new PML-dependent, p53-regulatory pathway for apoptosis and shed new light on the function of PML in tumour suppression.

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Figure 1: DNA-damage-induced apoptosis is reduced in PML−/− thymocytes.
Figure 2: PML enhances p53 transcriptional activation.
Figure 3: Transcriptional activity of p53 is impaired in PML−/− cells.
Figure 4: PML interacts with p53 in vitro and in vivo.
Figure 5: p53, CBP and PML co-localize in the PML-NB.
Figure 6: Function of PML-NB localization in transcriptional co-activation by PML.
Figure 7: Impaired p53–DNA binding and induction of p53 target genes in PML−/− thymocytes.

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Acknowledgements

We thank C. Prives, K. Scotto, R. Johnson, P. Freemont, K. Elkon, L. Longo, K. Manova, Z. G. Wang, V. Richon and J. Hung for materials, advice and help in some experiments. We are grateful to A. Levine for useful discussions. P.S. is a recipient of a doctorate fellowship from the University of Modena, Italy. P.P.P. is a Scholar of the Leukemia and Lymphoma Society of America (previously know as the Leukemia Society of America). This work was supported by the Sloan-Kettering Institute (CA-08748) and NIH (CA 71692 awarded to P.P.P.).

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Authors and Affiliations

  1. Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Ailan Guo, Paolo Salomoni, Alan Shih, Sue Zhong & Pier Paolo Pandolfi

  2. Institute of Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, 10032, New York, USA

    Jianyuan Luo & Wei Gu

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  1. Ailan Guo
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Correspondence to Pier Paolo Pandolfi.

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Guo, A., Salomoni, P., Luo, J. et al. The function of PML in p53-dependent apoptosis. Nat Cell Biol 2, 730–736 (2000). https://doi.org/10.1038/35036365

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