Division of Pathology and Experimental Medicine, Graduate School of Life Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto-shi 861-8556, Japan.
Biochem Biophys Res Commun. 2010 Sep 24;400(3):426-31. doi: 10.1016/j.bbrc.2010.08.094. Epub 2010 Aug 27.
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.
细胞周期蛋白 D1 的转录功能，其失调经常在人类癌症中观察到，被认为有助于癌症的形成。在本研究中，我们表明细胞周期蛋白 D1 蛋白通过直接与其结合并干扰其与肺癌细胞中 p300 相互作用来抑制 RUNX3 活性。细胞周期蛋白 D1 抑制 p300 依赖性 RUNX3 乙酰化，并负调控细胞周期蛋白依赖性激酶 (cdk) 抑制剂 p21 的表达。细胞周期蛋白 D1 的这些转录作用不需要 cdk4/6 激酶的激活。我们提出，细胞周期蛋白 D1 提供了一个转录开关，允许 RUNX3 的肿瘤抑制活性在癌细胞中被抑制。由于 RUNX3 在广泛的癌症中发挥肿瘤抑制作用，因此非典型细胞周期蛋白 D1 功能对于 RUNX3 调节增殖的上皮细胞的肿瘤转化可能至关重要。
