14-3-3β Binds to and Negatively Regulates the Tuberous Sclerosis Complex 2 (TSC2) Tumor Suppressor Gene Product, Tuberin
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TSC2, or tuberin, is the product of the tuberous sclerosis tumor suppressor gene TSC2 and acts downstream of the phosphatidylinositol 3-kinase-Akt signaling pathway to negatively regulate cellular growth. One mechanism underlying its function is to assemble into a heterodimer with the TSC1 gene product TSC1, or hamartin, resulting in a reduction in phosphorylation, and hence activation, of the ribosomal subunit S6 kinase (S6K). We identified a novel interaction between TSC2 and 14-3-3beta. We found that 14-3-3beta does not interfere with TSC1-TSC2 binding and can form a ternary complex with these two proteins. Association between 14-3-3beta and TSC2 requires phosphorylation of TSC2 at a unique residue that is not a known Akt phosphorylation site. The overexpression of 14-3-3beta compromises the ability of the TSC1-TSC2 complex to reduce S6K phosphorylation. The antagonistic activity of 14-3-3beta toward TSC is dependent on the 14-3-3beta-TSC2 interaction, since a mutant of TSC2 that is not recognized by 14-3-3beta is refractory to 14-3-3beta. We suggest that 14-3-3 proteins interact with the TSC1-TSC2 complex and negatively regulate the function of the TSC proteins.
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TSC2 has been shown to interact with 14-3-3 proteins when phosphorylated, and this interaction disrupts the function of the TSC1-TSC2 complex.
“Notably, TSC2 has already been shown to interact with 143-3 proteins when phosphorylated, and that this interaction disrupts the function of the TSC1-TSC2 complex (Nellist et al., 2003;Shumway et al., 2003).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Shumway et al., 2003
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- Authors
- Shumway, S. D., Li, Y., & Xiong, Y.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Michigan (US)
- Corresponding author
- Xiong, Yue
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 278
- Issue
- 4
- Pages
- 2089-2092
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2085381292
- Cited by
- 74
- References
- 18
- Citations by year
- 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2014: 5 · 2012: 3
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA065572, CA 65572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- 14-3-3β, tuberin, TSC2, TSC1, hamartin, tuberous sclerosis complex, protein-protein interaction, ternary complex, Akt signaling, phosphatidylinositol 3-kinase, RSK, S6K phosphorylation, tumor suppressor regulation, protein phosphorylation
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Binding Sites, Cell Line, Gene Expression Regulation, Glutathione Transferase, Humans, Phosphorylation, Plasmids, Precipitin Tests, Protein Binding, Proteins, Recombinant Fusion Proteins, Repressor Proteins, Tumor Cells, Cultured, Tyrosine 3-Monooxygenase, Blotting, Western, Signal Transduction, Genes, Tumor Suppressor, Ribosomal Protein S6 Kinases, Two-Hybrid System Techniques, Tumor Suppressor Proteins, 14-3-3 Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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