14-3-3beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin.

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.
Mesh Terms:
14-3-3 Proteins, Binding Sites, Blotting, Western, Cell Line, Gene Expression Regulation, Genes, Tumor Suppressor, Glutathione Transferase, Humans, Phosphorylation, Plasmids, Precipitin Tests, Protein Binding, Proteins, Recombinant Fusion Proteins, Repressor Proteins, Ribosomal Protein S6 Kinases, Signal Transduction, Tumor Cells, Cultured, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Tyrosine 3-Monooxygenase
J. Biol. Chem.
Date: Jan. 24, 2003
Download Curated Data For This Publication
Switch View:
  • Interactions 3