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.
Rokudai
Susumu
S
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Aikawa
Yukiko
Y
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Tagata
Yusuke
Y
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Tsuchida
Nobuo
N
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Taya
Yoichi
Y
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Kitabayashi
Issay
I
Molecular Oncology Division, Radiobiology Division, National Cancer Center Research Institute, Tokyo 104-0045 and the Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan. Electronic address: ikitabay@ncc.go.jp.
D000818:Animals; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology*; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011993:Recombinant Fusion Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human; C511438:MOZ protein, mouse