Binding of p53 to the central domain of Mdm2 is regulated by phosphorylation.
The Mdm2 protein is the major regulator of the tumor suppressor protein p53. We show that the p53 protein associates both with the N-terminal and with the central domain of Mdm2. The central p53-binding site of Mdm2 encompasses amino acids 235-300. Binding of p53 to the central domain is significantly enhanced after phosphorylation of the central domain of Mdm2. The N-terminal and central domains of Mdm2 act synergistically in binding to p53. p53 mutants that have mutations in the tetramerization domain and that fail to oligomerize do not show such an enhancement of binding in the presence of the other binding site.
Kulikov
Roman
R
Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, 76021 Karlsruhe, Germany.
Winter
Markus
M
Blattner
Christine
C
D000107:Acetylation; D001665:Binding Sites; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D018076:DNA, Complementary; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D005982:Glutathione Transferase