Structure and promoter analysis of murine CAD and ICAD genes

Kohki Kawane, Hidehiro Fukuyama, Masashi Adachi, Hideki Sakahira, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkin, Shigekazu Nagata

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalCell death and differentiation
Volume6
Issue number8
DOIs
StatePublished - Aug 1999

Keywords

  • Alternative splicing
  • Apoptosis
  • CAD
  • Expression
  • ICAD
  • Promoter

ASJC Scopus subject areas

  • Cell Biology

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