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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-11-3499. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3499v1 102/5/1788    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, Q.-L. Articles by Muraguchi, A. Search for Related Content PubMed PubMed Citation Articles by Liu, Q.-L. Articles by Muraguchi, A. Related Collections Immunobiology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1788-1796 IMMUNOBIOLOGY Heat shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimulated T cells Qing-Li Liu, Hiroyuki Kishi, Kenzo Ohtsuka, and Atsushi Muraguchi From the Department of Immunology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan; and the Laboratory of Cell & Stress Biology, Department of Environmental Biology, College of Bioscience & Biotechnology, Chubu University, Matsumoto-cho, Kasugai, Aichi, Japan. DNA fragmentation is a hallmark of cells undergoing apoptosis and is mediated mainly by the caspase-activated DNase (CAD or DNA-fragmentation factor 40 [DFF40]), which is activated when released from its inhibitor protein (ICAD or DFF45) upon apoptosis signals. Here we analyzed the effect of heat shock protein 70 (Hsp70) on CAD activity in T-cell receptor (TCR)–induced apoptosis using a T-cell line (TAg-Jurkat). Overexpression of Hsp70 significantly augmented the apoptotic cell death as well as DNA fragmentation in CD3/CD28- or staurosporine-stimulated cells. Following stimulation of cells with CD3/CD28 or staurosporine, Hsp70 was coprecipitated with free CAD, but not with CAD associated with ICAD. Furthermore, the purified Hsp70 dose-dependently augmented DNA-fragmentation activity of caspase-3–activated CAD in a cell-free system. Peptide-binding domain–deleted Hsp70 could neither bind nor augment its activity, while adenosine triphosphate (ATP)–binding domain–deleted Hsp70 or the peptide-binding domain itself bound CAD and augmented its activity. These results indicate that the the binding of Hsp70 to the activated CAD via the peptide-binding domain augments its activity. Although CAD lost its activity in an hour after being released from ICAD in vitro, its activity was retained after an hour of incubation in the presence of Hsp70, suggesting that Hsp70 may be involved in stabilization of CAD activity. Finally, CAD that had been coprecipitated with Hsp70 from the cell lysate of staurosporine-activated 293T cells induced chromatin DNA fragmentation and its activity was not inhibited by ICAD. These results suggest that Hsp70 binds free CAD in TCR-stimulated T cells to stabilize and augment its activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Schmitt, M. Gehrmann, M. Brunet, G. Multhoff, and C. Garrido Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy J. Leukoc. Biol., January 1, 2007; 81(1): 15 - 27. [Abstract] [Full Text] [PDF] D. Lechardeur, S. Dougaparsad, C. Nemes, and G. L. Lukacs Oligomerization State of the DNA Fragmentation Factor in Normal and Apoptotic Cells J. Biol. Chem., December 2, 2005; 280(48): 40216 - 40225. [Abstract] [Full Text] [PDF] R. Ran, A. Lu, L. Zhang, Y. Tang, H. Zhu, H. Xu, Y. Feng, C. Han, G. Zhou, A. C. Rigby, et al. Hsp70 promotes TNF-mediated apoptosis by binding IKK{gamma} and impairing NF-{kappa}B survival signaling Genes & Dev., June 15, 2004; 18(12): 1466 - 1481. [Abstract] [Full Text] [PDF] H. M. Beere `The stress of dying': the role of heat shock proteins in the regulation of apoptosis J. Cell Sci., June 1, 2004; 117(13): 2641 - 2651. [Abstract] [Full Text] [PDF]

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