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ATF2 - at the crossroad of nuclear and cytosolic functions

Eric Lau1, Ze'ev A Ronai

  • 1Signal Transduction Program, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Rd, La Jolla, CA 92130, USA. elau@sbmri.org

Journal of Cell Science
|June 12, 2012
PubMed

Insights

Activating transcription factor 2 (ATF2) has dual roles in cancer, acting as an oncogene or tumor suppressor based on its location. Protein kinase C epsilon (PKCε) controls ATF2

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Transcription factors exhibit context-dependent oncogenic or tumor suppressor activities.
  • Activating transcription factor 2 (ATF2) demonstrates opposing functions in different cancers.
  • Subcellular localization of ATF2 is critical for its diverse roles.

Purpose of the Study:

  • To summarize the regulation and function of ATF2 in both nuclear and cytosolic compartments.
  • To elucidate the role of protein kinase C epsilon (PKCε) in controlling ATF2 localization and function.
  • To present a novel mechanism for 'oncogene addiction' involving ATF2 regulation.

Main Methods:

  • Review of existing literature on ATF2 function and regulation.
  • Analysis of ATF2's role in transcription, DNA damage response, and cell death pathways.
  • Investigation of ATF2 translocation to the cytosol under genotoxic stress.

Main Results:

  • Nuclear ATF2 is involved in global transcription and DNA damage response.
  • Cytosolic ATF2 impairs mitochondrial function and promotes cell death.
  • PKCε-mediated phosphorylation acts as a key regulator of ATF2 subcellular localization and activity.

Conclusions:

  • ATF2's opposing functions are dictated by its subcellular localization.
  • PKCε phosphorylation is a master switch for ATF2's dual roles.
  • Regulation of ATF2 localization offers a new paradigm for targeting oncogene addiction.

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