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  • Original Paper
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Genetic dissection of c-myc apoptotic pathways

Oncogene volume 19, pages 3200–3212 (2000)Cite this article

Abstract

All biological functions mediated by the c-myc oncoprotein require an intact transactivation domain (TAD). We compared TAD mutants for their ability to promote apoptosis of 32D myeloid cells in response to interleukin-3 (IL-3) deprivation and exposure to chemotherapeutic drugs, and to activate ornithine decarboxylase, an endogenous c-myc target. Different sub-regions of the TAD were required to mediate each function. cDNA microarrays were then used to identify multiple c-myc-regulated transcripts, some of which were also modulated by IL-3 or cytotoxic drugs, as well as by specific sub-regions of the TAD. Several of the c-myc-regulated transcripts had also been previously identified as targets for IFN-γ. The functional consequences of their deregulation were manifested by a marked sensitivity of c-myc-overexpressing cells to IFN-γ-mediated apoptosis. Our results establish that several well-characterized functions of c-myc are separable and correlate with the expression of a novel group of target genes, some of which also mediate the apoptotic action of IFN-γ.

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Acknowledgements

We thank Paula Pitha and Doug Hilton for cDNA probes and Karoly Marnics for valuable discussions. This work was supported by NIH grants HL33741 and CA78259 to EV Prochownik and by a Children's Hospital of Pittsburgh Research Advisory Post-Doctoral Fellowship to JMTersak.

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Authors and Affiliations

  1. Section of Hematology/Oncology, The Children's Hospital of Pittsburgh, Pittsburgh, 15213, Pennsylvania, PA, USA

    Chadd E Nesbit, Jean M Tersak, Linette E Grove, Amy Drzal & Edward V Prochownik

  2. The Department of Molecular Genetics and Biochemistry, The University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, PA, USA

    Hyunjung Choi & Edward V Prochownik

  3. The Program in Molecular Oncology, The University of Pittsburgh Cancer Institute, Pittsburgh, 15213, Pennsylvania, PA, USA

    Edward V Prochownik

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  1. Chadd E Nesbit
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Nesbit, C., Tersak, J., Grove, L. et al. Genetic dissection of c-myc apoptotic pathways. Oncogene 19, 3200–3212 (2000). https://doi.org/10.1038/sj.onc.1203636

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