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 journalArticlepeer-review

55 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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