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Activation of GCN2 in UV-irradiated cells inhibits translation

Jing Deng1, Heather P Harding, Brian Raught

  • 1Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada.

Current Biology : CB
|August 15, 2002
PubMed
Abstract

Insights

UV irradiation triggers translation repression in mammalian cells by activating the GCN2 kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2alpha). This pathway is crucial for the cellular response to UV stress.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Biochemistry

Background:

  • Mammalian cells suppress DNA replication, transcription, and mRNA translation upon UV irradiation.
  • Mechanisms of UV-induced translational repression remain largely unknown.
  • Prior research focused on DNA replication and transcription, neglecting translation.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying UV-induced translational repression.
  • To identify key proteins and pathways involved in inhibiting mRNA translation post-UV exposure.

Main Methods:

  • Utilized GCN2 knockout (GCN2-/-) cells.
  • Employed cells expressing non-phosphorylatable eIF2alpha.
  • Analyzed the impact of UV irradiation on protein synthesis and eIF2alpha phosphorylation.
  • Investigated the roles of SAPK/JNK and p38 MAP kinase pathways.

Main Results:

  • UV irradiation induces phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2alpha).
  • This phosphorylation is mediated by the GCN2 kinase, independent of SAPK/JNK or p38 MAP kinase.
  • GCN2-/- cells and cells with non-phosphorylatable eIF2alpha cannot repress translation following UV irradiation.

Conclusions:

  • Established a mechanism for UV-induced translation inhibition involving GCN2-mediated eIF2alpha phosphorylation.
  • Identified a novel role for mammalian GCN2 in mediating cellular responses to UV stress.
  • Highlighted the importance of translational control in DNA damage response pathways.

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