Regulation of nucleolar signalling to p53 through NEDDylation of L11
Open accessAbstract
Several studies have shown that ribosomal proteins (RPs) are important mediators of p53 activation in response to nucleolar disruption; however, the pathways that control this signalling function of RPs are currently unknown. We have recently shown that RPs are targets for the ubiquitin-like molecule NEDD8, and that NEDDylation protects RPs from destabilization. Here, we identify NEDD8 as a crucial regulator of L11 RP signalling to p53. A decrease in L11 NEDDylation during nucleolar stress causes relocalization of L11 from the nucleolus to the nucleoplasm. This not only provides the signal for p53 activation, but also makes L11 susceptible to degradation. Mouse double minute 2 (MDM2) -mediated NEDDylation protects L11 from degradation and this is required for p53 stabilization during nucleolar stress. By controlling the correct localization and stability of L11, NEDD8 acts as a crucial, new regulator of nucleolar signalling to p53.
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Mdm2 can facilitate transfer of Ubl molecules to p53 and to other substrates.
“The discovery that Mdm2 can facilitate transfer of these Ubl molecules to p53, and to other substrates [125] adds additional layers of complexity to p53 regulation.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [125]
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- Authors
- Sundqvist, A., Liu, G., Mirsaliotis, A., & Xirodimas, D. P.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Xirodimas, Dimitris P
- Venue
- The EMBO Reports
- Published
- 2009-08-28
- Volume
- 10
- Issue
- 10
- Pages
- 1132-1139
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC2759733
- OpenAlex
- W2160411656
- Cited by
- 132
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 10 · 2023: 2 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 3 · 2014: 13 · 2013: 11 · 2012: 15
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- neddylation, NEDD8, ribosomal protein L11, p53 activation, nucleolar stress, MDM2, protein stability, protein localization, ubiquitin-like modification, ribosomal proteins
- MeSH terms
- NEDD8 Protein, Animals, Cell Nucleolus, Humans, Ribosomal Proteins, Ubiquitins, Signal Transduction, Tumor Suppressor Protein p53, Active Transport, Cell Nucleus, Cell Line, Tumor, Mice, Proto-Oncogene Proteins c-mdm2
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