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NEDDylation regulates E2F-1-dependent transcription

Sarah J Loftus1, Geng Liu, Simon M Carr

  • 1Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Old Road Campus off Roosevelt Drive, Oxford OX3 7DQ, UK.

EMBO Reports
|July 28, 2012
PubMed

Insights

The study shows that NEDD8 modifies the E2F-1 transcription factor, reducing its stability and activity. This reveals a new regulatory pathway impacting cell growth and transcription.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The ubiquitin-like molecule NEDD8 is known to modify cullin-RING ubiquitin E3 ligases.
  • The role of NEDD8 in modifying non-cullin substrates and its functional significance are not fully understood.

Purpose of the Study:

  • To investigate whether the cell-cycle-regulating transcription factor E2F-1 is a substrate for NEDD8 post-translational modification.
  • To elucidate the functional consequences of E2F-1 NEDDylation.

Main Methods:

  • Western blotting to detect NEDDylation of E2F-1.
  • Quantitative PCR and reporter assays to assess transcriptional activity.
  • Cell growth assays to evaluate the impact on proliferation.

Main Results:

  • E2F-1 was identified as a novel substrate for NEDD8 modification (NEDDylation).
  • NEDDylation of E2F-1 led to decreased protein stability and reduced transcriptional activity.
  • The modification resulted in slower cell growth, indicating a functional impact on cell cycle regulation.
  • Lysine residues targeted by NEDDylation were also found to be methylated, suggesting cross-talk between modifications.

Conclusions:

  • NEDD8 directly regulates the stability and function of the transcription factor E2F-1.
  • This study uncovers a new mechanism for controlling E2F-1 activity, impacting cell growth.
  • The findings highlight an expanding role for NEDD8 in post-translational regulation of transcription factors.

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