TY - JOUR
T1 - Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest
AU - Rokudai, Susumu
AU - Aikawa, Yukiko
AU - Tagata, Yusuke
AU - Tsuchida, Nobuo
AU - Taya, Yoichi
AU - Kitabayashi, Issay
PY - 2009/1/2
Y1 - 2009/1/2
N2 - 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 Gl 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.
AB - 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 Gl 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.
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U2 - 10.1074/jbc.M805101200
DO - 10.1074/jbc.M805101200
M3 - Article
C2 - 19001415
AN - SCOPUS:58649114520
SN - 0021-9258
VL - 284
SP - 237
EP - 244
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -