The regulation of DNAse activities in subcellular compartments of activated thymocytes

Takuya Nagata, Hiroyuki Kishi, Qin Li Liu, Tadashi Matsuda, Tsuneo Imanaka, Kazuhiro Tsukada, Dongchon Kang, Atsushi Muraguchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Thymocytes expressing self-reactive T-cell receptors (TCR) are eliminated in the thymus through a TCR-mediated signal. This cell death signal (negative selection) generates nuclear morphological change and DNA fragmentation in thymocytes. However, the pathway leading to DNA fragmentation of thymocytes following TCR engagement remains obscure. In this study, we investigated the localization and function of caspase-activated DNAse (CAD) and its inhibitor (ICAD) in thymocytes prior to or after in vivo TCR stimulation. We showed that CAD and ICAD are co-localized in microsome, nuclei and cytosol in unstimulated thymocytes. Following in vivo TCR engagement, ICAD located in cytosol and microsome was degraded and the resulting activated CAD induced chromosomal DNA fragmentation. CAD present in cytosol and microsome of unstimulated thymocytes was activated by recombinant caspase-3, and microsomal CAD was released to the cytosol. These results demonstrate that TCR engagement of thymocytes induces caspase-3-dependent activation of CAD localized in both cytosol and microsome, leading to DNA fragmentation in harmony.

Original languageEnglish
Pages (from-to)399-406
Number of pages8
JournalImmunology
Volume105
Issue number4
DOIs
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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