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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.

SUBMITTER: Loftus SJ

PROVIDER: S-EPMC3432805 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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NEDDylation regulates E2F-1-dependent transcription.

Loftus Sarah J SJ Liu Geng G Carr Simon M SM Munro Shonagh S La Thangue Nicholas B NB

EMBO reports 20120727 9

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 ...[more]

PMID: 22836579

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