Phosphorylation of HDM2 by Akt
Abstract
The HDM2 protein is a key regulator of the tumour suppressor, p53. Control of HDM2 function is critical for normal cell proliferation and stress responses, and it is becoming evident that multiple modifications of HDM2 can regulate its function within cells. In this study we show that HDM2 associated with the serine-threonine kinase, Akt, in response to growth factor stimulation of human primary cells. This association was concurrent with phosphorylation of Akt (at Ser 473), and resulted in elevated expression of HDM2 and enhanced nuclear localization. However, analysis of HDM2 proteins mutated at the consensus Akt recognition sites at serines 166 and 186 indicated that modification at these residues was not sufficient for the increased expression of the protein, which was blocked by the PI3 kinase inhibitor LY294002. Tryptic peptide and mutational analyses revealed evidence for an Akt phosphorylation site in HDM2 additional to the two consensus sites.
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Both endogenous Mdm2 and transfected Mdm2 were exclusively located in the nucleus independent of phosphorylation status of Mdm2.
“both endogenous Mdm2 (Fig. 5A and Fig. 6, B and C) and transfected Mdm2 (31,51,60) were exclusively located in the nucleus independent of phosphorylation status of Mdm2.”
From Stabilization of Mdm2 via Decreased Ubiquitination Is Mediated by Protein Kinase B/Akt-dependent Phosphorylation (2004) · cites this paper as [60]
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- Authors
- Ashcroft, M., Ludwig, R. L., Woods, D. B., Copeland, T. D., Weber, H. O., MacRae, E. J., & Vousden, K. H.
- Affiliations
- Institute of Cancer Research (GB)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Vousden, Karen H
- Venue
- Oncogene
- Published
- 2002-03-21
- Volume
- 21
- Issue
- 13
- Pages
- 1955-1962
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2085058707
- Semantic Scholar
- 985529eeaa44b3cf9bd72cf21ff1eacb392635ac
- Cited by
- 197
- References
- 38
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 8 · 2017: 1 · 2016: 6 · 2015: 3 · 2014: 10 · 2013: 7 · 2012: 5
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- MDM2, Akt, protein phosphorylation, p53, tumor suppressor regulation, PI3-kinase, LY294002, nuclear localization, growth factor stimulation, protein-protein interaction
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Amino Acid Sequence, Cell Line, Chromatography, High Pressure Liquid, Enzyme Activation, Humans, Molecular Sequence Data, Mutation, Nuclear Proteins, Phosphorylation, Phosphoserine, Protein Binding, Proto-Oncogene Proteins, Transfection, Mutagenesis, Site-Directed, Consensus Sequence, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-mdm2
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