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NEDDylation controls the target specificity of E2F1 and apoptosis induction

I Aoki1, M Higuchi, Y Gotoh

  • 1Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.

Oncogene
|September 25, 2012
PubMed

Insights

Ubiquitin-like modifier NEDD8 regulates the transcription factor E2F1

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Transcription factor E2F1 is crucial for cell proliferation and apoptosis.
  • E2F1's role in apoptosis activation is not fully understood.
  • E2F1 is a significant molecular target in cancer therapy.

Purpose of the Study:

  • To elucidate the mechanism of E2F1 apoptotic function activation.
  • To investigate the role of NEDDylation in E2F1 activity and target specificity.
  • To explore the potential of targeting E2F1 modification for cancer treatment.

Main Methods:

  • Investigated covalent conjugation of E2F1 with NEDD8.
  • Utilized SENP8 (NEDD8-specific protease) overexpression and knockdown.
  • Assessed E2F1 transactivation activity at p73 and E2F2 genes.
  • Analyzed E2F1 interaction with Microcephalin 1.

Main Results:

  • E2F1 is covalently modified by NEDD8.
  • SENP8 overexpression de-NEDDylated E2F1, enhancing p73 gene transactivation.
  • SENP8 knockdown reduced p73 expression and E2F1/DNA damage-induced apoptosis.
  • SENP8 promoted E2F1 interaction with Microcephalin 1, crucial for p73 induction.

Conclusions:

  • NEDDylation acts as a molecular trigger, altering E2F1 target specificity.
  • This modification impacts E2F1's regulation of apoptosis.
  • Findings suggest implications for E2F1-targeted cancer therapies.

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