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NUB1 promotes cytoplasmic localization of p53 through cooperation of the NEDD8 and ubiquitin pathways

Oncogene volume 29, pages 2252–2261 (2010)Cite this article

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Abstract

Non-covalent recognition of ubiquitin (Ub) and ubiquitin-like molecules (Ubls) by interacting proteins has an important role in the regulation of protein function and initiation of signalling events. In addition, growing evidence suggests that regulation of p53 subcellular localization contributes to the biological outcome of the p53 response. Cytoplasmic p53 is shown to promote apoptosis and inhibit the induction of autophagy. In this study we show that NEDD8 ultimate buster 1 (NUB1), a non-covalent interactor of the Ubl NEDD8 (neural precursor cell expressed, developmentally downregulated 8), controls the localization of p53. Expression of NUB1 leads to decreased modification of p53 with NEDD8 and stimulation of p53 ubiquitination. The biological outcome is the cytoplasmic localization and inhibition of the transcriptional activity of p53. Although the effects of NUB1 on p53 depend on NEDDylation and the murine double minute 2 (Mdm2) E3-ligase, the cooperation of NEDD8 with ubiquitin is required. The data identify a role for NEDD8 in controlling p53 localization and suggest that NEDD8 can control protein function through its non-covalent recognition by interacting proteins.

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Acknowledgements

We thank Drs Kamitani, Bourdon and Saville for reagents. We also thank Neil Hattersley for help with the immunofluorescence experiments. The work is supported by the Association for International Cancer Research (AICR). DPX is an AICR Research Fellow.

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  1. Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK

    G Liu & D P Xirodimas

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  1. G Liu
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Correspondence to D P Xirodimas.

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Liu, G., Xirodimas, D. NUB1 promotes cytoplasmic localization of p53 through cooperation of the NEDD8 and ubiquitin pathways. Oncogene 29, 2252–2261 (2010). https://doi.org/10.1038/onc.2009.494

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