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  • Original Paper
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PML interacts with Myc, and Myc target gene expression is altered in PML-null fibroblasts

Oncogene volume 24, pages 2195–2203 (2005)Cite this article

Abstract

c-myc is a well-known proto-oncogene encoding for a transcription factor that needs to be tightly regulated in order to preserve cell homeostasis. The Promyelocytic Leukaemia gene product PML plays an important role in cell growth and survival, and resides in discrete subnuclear structures called Nuclear Bodies (NB). We performed comparative analysis of the expression of 40 Myc target genes and of Myc binding to their regulatory regions both in wild-type and PML knockout cells. We demonstrate that if PML is absent, despite Myc binding to the DNA regulatory sequences is unchanged, the expression profile of several Myc target genes is altered. PML is largely involved in gene regulation, via recruitment of several transcription factors and cofactors to the NB. Consistently, we show that Myc partially localizes to the NB and physically interacts with PML, and that this localization depends on Myc expression levels. As deregulation occurs to both activated and repressed Myc target genes, we propose that PML influences Myc transcriptional activity through a mechanism that involves the control of Myc post-translational modifications.

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Acknowledgements

We are grateful to PG Pelicci for providing reagents. We thank Salvatore Arbucci for confocal microscopy assistance, Valerio Orlando and Massimo Zollo for helpful suggestions, Graciana Diex-Roux, Alexandre Reymond, Giuseppe Merla, Giovanna Giorgio, Elena Rugarli, and Gilda Cobellis for critical reading of the manuscript, and Jonah Hershowitz for editing the manuscript. This work was supported by the Italian Telethon Foundation, and by an FIRC (Fondazione Italiana per la Ricerca sul Cancro) fellowship to SC.

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Author notes

  1. Francesca De Falco

    Present address: Federico II University, 80131, Napoli, Italy

  2. Paolo Salomoni

    Present address: MRC Toxicology Unit, Hodgkin Building University of Leicester, LE1 9HN, Leicester, UK

Authors and Affiliations

  1. Telethon Institute of Genetics and Medicine (TIGEM), 80131, Naples, Italy

    Stefano Cairo, Francesca De Falco, Mariateresa Pizzo & Germana Meroni

  2. Molecular Biology Program and Department of Pathology, Memorial Sloan Kettering Cancer Center, Sloan-Kettering Division, Cornell University, New York, NY, 10021, USA

    Paolo Salomoni & Pier Paolo Pandolfi

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  1. Stefano Cairo
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Correspondence to Germana Meroni.

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Cairo, S., De Falco, F., Pizzo, M. et al. PML interacts with Myc, and Myc target gene expression is altered in PML-null fibroblasts. Oncogene 24, 2195–2203 (2005). https://doi.org/10.1038/sj.onc.1208338

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