Kawane K, Fukuyama H, Adachi M, Sakahira H, Copeland N G, Gilbert D J, Jenkin N A, Nagata S
Department of Genetics, Osaka University Medical School, Osaka, Japan.
Cell Death Differ. 1999 Aug;6(8):745-52. doi: 10.1038/sj.cdd.4400547.
Caspase-activated DNase (CAD) degrades chromosomal DNA during apoptosis, whereas ICAD (inhibitor of CAD) inhibits the CAD's DNase by binding to it. Here, we describe the assignment of murine CAD and ICAD genes to the distal part of murine chromosome 4. Molecular cloning and structural analysis indicated that CAD and ICAD genes are comprised of 7 and 6 exons, respectively. Two different ICAD mRNAs coding for two forms of ICAD proteins (ICAD-S and ICAD-L) were found to be produced by alternative splicing of intron 5. The CAD and ICAD mRNAs were detected ubiquitously in various murine tissues. Analyses of the promoter activity with a series of deletion mutants of their 5' flanking regions indicated that a 190-bp 5' flanking region of the CAD gene was sufficient to promote the transcription. Whereas, a 120-bp flanking region of ICAD gene was required to promote its transcription. These regions do not show similarity between CAD and ICAD genes, suggesting that expression of CAD and ICAD genes is regulated by different mechanisms.
半胱天冬酶激活的脱氧核糖核酸酶（CAD）在细胞凋亡过程中降解染色体DNA，而ICAD（CAD抑制剂）通过与CAD结合来抑制其脱氧核糖核酸酶活性。在此，我们描述了将小鼠CAD和ICAD基因定位到小鼠4号染色体远端。分子克隆和结构分析表明，CAD和ICAD基因分别由7个和6个外显子组成。通过对内含子5的可变剪接发现，产生了两种编码两种形式ICAD蛋白（ICAD-S和ICAD-L）的不同ICAD mRNA。CAD和ICAD mRNA在各种小鼠组织中均有广泛检测。对其5'侧翼区域一系列缺失突变体的启动子活性分析表明，CAD基因190 bp的5'侧翼区域足以促进转录。而ICAD基因则需要120 bp的侧翼区域来促进其转录。这些区域在CAD和ICAD基因之间没有显示出相似性，这表明CAD和ICAD基因的表达受不同机制调控。
