Li Y, Xie M, Yang J, Yang D, Deng R, Wan Y, Yan B
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, 02881, USA.
Oncogene. 2006 Jun 1;25(23):3296-306. doi: 10.1038/sj.onc.1209363. Epub 2006 Feb 6.
Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor-normal tissues, survivin and DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression of DEC1 in stable lines proportionally increased the expression of survivin. In reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2 promoter. In contrast to the repression, the activation was delayed and varied depending on serum concentrations and cycle blockers. Studies with reporter mutants located, in the survivin promoter, two Sp1 sites that supported DEC1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation detected the presence of DEC1 in the survivin promoter. These findings establish that the survivin gene is a transcription target of DEC1, and induction of survivin is at least in part responsible for DEC1 antiapoptosis.
人类软骨细胞差异表达基因（DEC）、经视黄酸刺激的小鼠以及大鼠分裂和毛发相关蛋白构成了一类结构独特的碱性螺旋-环-螺旋蛋白。DEC1在肿瘤中大量表达，并能保护细胞免受血清饥饿诱导的凋亡。在本研究中，我们报道DEC1的抗凋亡作用是通过诱导抗凋亡蛋白survivin实现的。在配对的肿瘤-正常组织中，survivin和DEC1呈现平行的表达模式。在稳定细胞系中，四环素诱导的DEC1表达成比例地增加了survivin的表达。在报告基因检测中，DEC1反式激活了survivin启动子，但抑制了DEC2启动子。与抑制作用相反，激活作用延迟且因血清浓度和细胞周期阻滞剂而异。对survivin启动子中报告基因突变体的研究发现了两个支持DEC1反式激活的Sp1位点。电泳迁移率变动分析和染色质免疫沉淀检测到DEC1存在于survivin启动子中。这些发现表明survivin基因是DEC1的转录靶点，survivin的诱导至少部分地介导了DEC1的抗凋亡作用。
