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  • Title: NEDDylation regulates E2F-1-dependent transcription.
    Author: Loftus SJ, Liu G, Carr SM, Munro S, La Thangue NB.
    Journal: EMBO Rep; 2012 Sep; 13(9):811-8. PubMed ID: 22836579.
    Abstract:
    The ubiquitin-like molecule NEDD8 modifies cullin-RING ubiquitin E3 ligases. NEDD8 has been shown to have a few additional substrates, but the extent to which this modification targets non-cullins and the functional significance of such modifications remain unclear. Here, we demonstrate that the cell-cycle-regulating transcription factor E2F-1 is a substrate for NEDD8 post-translational modification. NEDDylation results in decreased E2F-1 stability, lower transcriptional activity and slower cell growth. The lysine residues in E2F-1 targeted for NEDDylation can also be methylated, pointing to a possible interplay between these modifications. These results identify a new mode of E2F-1 regulation and highlight the emerging role of NEDD8 in regulating transcription factor stability and function.
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