Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest.
Upon DNA damage, p53 can induce either cell-cycle arrest or apoptosis. Here we show that monocytic leukemia zinc finger (MOZ) forms a complex with p53 to induce p21 expression and cell-cycle arrest. The levels of the p53-MOZ complex increased in response to DNA damage to levels that induce cell-cycle arrest. ... MOZ(-/-) mouse embryonic fibroblasts failed to arrest in G1 in response to DNA damage, and DNA damage-induced expression of p21 was impaired in MOZ(-/-) cells. These results suggest that MOZ is involved in regulating cell-cycle arrest in the G1 phase. Screening of tumor-associated p53 mutants demonstrated that the G279E mutation in p53 disrupts interactions between p53 and MOZ, but does not affect the DNA binding activity of p53. The leukemia-associated MOZ-CBP fusion protein inhibits p53-mediated transcription. These results suggest that inhibition of p53/MOZ-mediated transcription is involved in tumor pathogenesis and leukemogenesis.
Mesh Terms:
Animals, Cell Line, Cyclin-Dependent Kinase Inhibitor p21, Embryo, Mammalian, Fibroblasts, G1 Phase, Gene Expression Regulation, Histone Acetyltransferases, Humans, Mice, Mice, Knockout, Protein Binding, Recombinant Fusion Proteins, Tumor Suppressor Protein p53
Animals, Cell Line, Cyclin-Dependent Kinase Inhibitor p21, Embryo, Mammalian, Fibroblasts, G1 Phase, Gene Expression Regulation, Histone Acetyltransferases, Humans, Mice, Mice, Knockout, Protein Binding, Recombinant Fusion Proteins, Tumor Suppressor Protein p53
J. Biol. Chem.
Date: Jan. 02, 2009
PubMed ID: 19001415
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