Cyclin D-1 blocks the anti-proliferative function of RUNX3 by interfering with RUNX3-p300 interaction
Cyclin D-1 blocks the anti-proliferative function of RUNX3 by interfering with RUNX3-p300 interaction
复制标题
DOI：
10.1016/j.bbrc.2010.08.094
复制
发表时间：
2010-09-24
影响因子：
3.1
通讯作者：
Ito, Takaaki
中科院分区：
文献类型：
--
作者：
Iwatani, Kazunori;Fujimoto, Tetsuhiro;Ito, Takaaki
在肺癌细胞中，细胞周期蛋白D1通过直接与RUNX3结合并干扰其与p300的相互作用来抑制RUNX3的活性。Cyclin D1抑制依赖于p300的RUNX3乙酰化，负向调节细胞周期蛋白依赖的激酶(CDK)抑制p21的表达，这些细胞周期蛋白的转录作用不需要CDK4/6激活。我们认为，由于RUNX3在多种癌症中发挥抑瘤作用，细胞周期蛋白D1提供了一个转录开关，使RUNX3的抑癌活性在肿瘤细胞中受到抑制。非规范的细胞周期蛋白D1功能可能对RUNX3调控增殖的上皮细胞的肿瘤转化至关重要(C)2010爱思唯尔公司。保留所有权利。
Transcriptional function of cyclin D1, whose deregulation is frequently observed in human cancers, has been suggested to contribute to cancer formation In the present study, we show that cyclin D1 protein inhibits RUNX3 activity by directly binding to It and interfering with its interaction with p300 interaction in lung cancer cells Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively regulates cyclin-dependent kinase (cdk) inhibitor p21 expression These transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation We propose that cyclin D1 provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells Since RUNX3 plays tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1 function may be critical for neoplastic transformation of the epithelial cells in which RUNX3 regulates proliferation (C) 2010 Elsevier Inc. All rights reserved.