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EMBO Rep. 2012 Sep;13(9):811-8. doi: 10.1038/embor.2012.113. Epub 2012 Jul 27.

NEDDylation regulates E2F-1-dependent transcription.

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


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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