Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest

Susumu Rokudai, Yukiko Aikawa, Yusuke Tagata, Nobuo Tsuchida, Yoichi Taya, Issay Kitabayashi

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number1
DOIs
Publication statusPublished - 02-01-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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