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Structure and promoter analysis of murine CAD and ICAD genes

  1. Author:
    Kawane, K.
    Fukuyama, H.
    Adachi, M.
    Sakahira, H.
    Copeland, N. G.
    Gilbert, D. J.
    Jenkin, N. A.
    Nagata, S.

  2. Author Address

    Nagata S Osaka Univ, Med Sch B3, Dept Genet 2-2 Yamada Oka Osaka 5650871 Japan Osaka Univ, Med Sch B3, Dept Genet Osaka 5650871 Japan Japan Sci & Technol Corp, Core Res Evolut Sci & Technol Osaka 5650871 Japan NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Cell Death and Differentiation
    1. 6
    2. 8
    3. Pages: 745-752
  4. Type of Article: Article
  1. Abstract:

    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. [References: 29]

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