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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.

Original publication

DOI

10.1038/embor.2012.113

Type

Journal article

Journal

EMBO Rep

Publication Date

09/2012

Volume

13

Pages

811 - 818

Keywords

Cell Line, Tumor, Cell Proliferation, E2F1 Transcription Factor, Humans, Lysine, Methylation, NEDD8 Protein, Protein Stability, Transcription, Genetic, Ubiquitination, Ubiquitins