Genetic dissection of c-myc apoptotic pathways

Chadd Nesbit, Jean M. Tersak, Linette E. Grove, Amy Drzal, Hyunjung Choi, Edward V. Prochownik

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 subregions 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.

Original languageEnglish (US)
Pages (from-to)3200-3212
Number of pages13
JournalOncogene
Volume19
Issue number28
DOIs
StatePublished - Jun 29 2000

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Transcriptional Activation
Dissection
Interleukin-3
Apoptosis
Ornithine Decarboxylase
Oncogene Proteins
Myeloid Cells
Oligonucleotide Array Sequence Analysis
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Nesbit, C., Tersak, J. M., Grove, L. E., Drzal, A., Choi, H., & Prochownik, E. V. (2000). Genetic dissection of c-myc apoptotic pathways. Oncogene, 19(28), 3200-3212. https://doi.org/10.1038/sj.onc.1203636
Nesbit, Chadd ; Tersak, Jean M. ; Grove, Linette E. ; Drzal, Amy ; Choi, Hyunjung ; Prochownik, Edward V. / Genetic dissection of c-myc apoptotic pathways. In: Oncogene. 2000 ; Vol. 19, No. 28. pp. 3200-3212.
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Nesbit, C, Tersak, JM, Grove, LE, Drzal, A, Choi, H & Prochownik, EV 2000, 'Genetic dissection of c-myc apoptotic pathways', Oncogene, vol. 19, no. 28, pp. 3200-3212. https://doi.org/10.1038/sj.onc.1203636

Genetic dissection of c-myc apoptotic pathways. / Nesbit, Chadd; Tersak, Jean M.; Grove, Linette E.; Drzal, Amy; Choi, Hyunjung; Prochownik, Edward V.

In: Oncogene, Vol. 19, No. 28, 29.06.2000, p. 3200-3212.

Research output: Contribution to journalArticle

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Nesbit C, Tersak JM, Grove LE, Drzal A, Choi H, Prochownik EV. Genetic dissection of c-myc apoptotic pathways. Oncogene. 2000 Jun 29;19(28):3200-3212. https://doi.org/10.1038/sj.onc.1203636