title: NEDDylation regulates E2F-1-dependent transcription.
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.
authors: 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.
authors: Sarah J
authors: SJ
authors: Loftus
authors: Geng
authors: G
authors: Liu
authors: Simon M
authors: SM
authors: Carr
authors: Shonagh
authors: S
authors: Munro
authors: Nicholas B
authors: NB
authors: La Thangue
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D000075687:NEDD8 Protein; D055550:Protein Stability; D014158:Transcription, Genetic; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050687:E2F1 Transcription Factor; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins; D008239:Lysine