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Journal of Cellular Biochemistry

Fanconi anemia D2 protein is an apoptotic target mediated by caspases

Authors

  • Su-Jung Park,

    1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202
    2. Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
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  • Brian D. Beck,

    1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202
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  • M. Reza Saadatzadeh,

    1. Pediatrics and Wells Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
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  • Laura S. Haneline,

    1. Pediatrics and Wells Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
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  • D. Wade Clapp,

    1. Pediatrics and Wells Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
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  • Suk-Hee Lee

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202
    2. Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202
    • Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, 635 Barnhill Dr. Indianapolis, IN 46202.
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Abstract

FANCD2, a key factor in the FANC-BRCA1 pathway is monoubiquitinated and targeted to discrete nuclear foci following DNA damage. Since monoubiquitination of FANCD2 is a crucial indicator for cellular response to DNA damage, we monitored the fate of FANCD2 and its monoubiquitination following DNA damage. Disappearance of FANCD2 protein was induced following DNA damage in a dose-dependent manner, which correlated with degradation of BRCA1 and poly-ADP ribose polymerase (PARP), known targets for caspase-mediated apoptosis. Disappearance of FANCD2 was not affected by a proteasome inhibitor but was blocked by a caspase inhibitor. DNA damage-induced disappearance of FANCD2 was also observed in cells lacking FANCA, suggesting that disappearance of FANCD2 does not depend on FANC-BRCA1 pathway and FANCD2 monoubiquitination. In keeping with this, cells treated with TNF-α, an apoptotic stimulus without causing any DNA damage, also induced disappearance of FANCD2 without monoubiquitination. Together, our data suggest that FANCD2 is a target for caspase-mediated apoptotic pathway, which may be an early indicator for apoptotic cell death. J. Cell. Biochem. 112: 2383–2391, 2011. © 2011 Wiley-Liss, Inc.

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