单核细胞白血病锌指蛋白（MOZ）与p53相互作用，以诱导p21表达并使细胞周期停滞。

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

作者信息

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

机构信息

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.

出版信息

J Biol Chem. 2009 Jan 2;284(1):237-244. doi: 10.1074/jbc.M805101200. Epub 2008 Nov 10.

DOI:10.1074/jbc.M805101200

PMID:19001415

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 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.

摘要

DNA 损伤时，p53 可诱导细胞周期停滞或凋亡。在此我们表明，单核细胞白血病锌指蛋白（MOZ）与 p53 形成复合物以诱导 p21 表达并导致细胞周期停滞。p53-MOZ 复合物的水平会因 DNA 损伤而升高至诱导细胞周期停滞的水平。MOZ(-/-)小鼠胚胎成纤维细胞在 DNA 损伤时无法停滞在 G1 期，且 MOZ(-/-)细胞中 DNA 损伤诱导的 p21 表达受损。这些结果表明，MOZ 参与调控 G1 期的细胞周期停滞。对肿瘤相关 p53 突变体的筛选表明，p53 中的 G279E 突变会破坏 p53 与 MOZ 之间的相互作用，但不影响 p53 的 DNA 结合活性。白血病相关的 MOZ-CBP 融合蛋白会抑制 p53 介导的转录。这些结果表明，抑制 p53/MOZ 介导的转录与肿瘤发病机制和白血病发生有关。