Distinct Thresholds Govern Myc's Biological Output In Vivo

Daniel J. Murphy, Melissa R. Junttila, Laurent Pouyet, Anthony Karnezis, Ksenya Shchors, Duyen A. Bui, Lamorna Brown-Swigart, Leisa Johnson, Gerard I. Evan

Research output: Contribution to journalArticle

255 Scopus citations

Abstract

Deregulated Myc triggers a variety of intrinsic tumor suppressor programs that serve to restrain Myc's oncogenic potential. Since Myc activity is also required for normal cell proliferation, activation of intrinsic tumor suppression must be triggered only when Myc signaling is oncogenic. However, how cells discriminate between normal and oncogenic Myc is unknown. Here we show that distinct threshold levels of Myc govern its output in vivo: low levels of deregulated Myc are competent to drive ectopic proliferation of somatic cells and oncogenesis, but activation of the apoptotic and ARF/p53 intrinsic tumor surveillance pathways requires Myc overexpression. The requirement to keep activated oncogenes at a low level to avoid engaging tumor suppression is likely an important selective pressure governing the early stages of tumor microevolution.

Original languageEnglish (US)
Pages (from-to)447-457
Number of pages11
JournalCancer Cell
Volume14
Issue number6
DOIs
StatePublished - Dec 9 2008
Externally publishedYes

    Fingerprint

Keywords

  • CELLBIO
  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Murphy, D. J., Junttila, M. R., Pouyet, L., Karnezis, A., Shchors, K., Bui, D. A., Brown-Swigart, L., Johnson, L., & Evan, G. I. (2008). Distinct Thresholds Govern Myc's Biological Output In Vivo. Cancer Cell, 14(6), 447-457. https://doi.org/10.1016/j.ccr.2008.10.018