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    Cell. 2003 Mar 7;112(5):659-72.

    Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor.

    Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J.

    Center for Blood Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.

    Erratum in:

    • Cell. 2003 Oct 17;115(2):241.

    Comment in:

    Granzyme A (GzmA) induces a caspase-independent cell death pathway characterized by single-stranded DNA nicks and other features of apoptosis. A GzmA-activated DNase (GAAD) is in an ER associated complex containing pp32 and the GzmA substrates SET, HMG-2, and Ape1. We show that GAAD is NM23-H1, a nucleoside diphosphate kinase implicated in suppression of tumor metastasis, and its specific inhibitor (IGAAD) is SET. NM23-H1 binds to SET and is released from inhibition by GzmA cleavage of SET. After GzmA loading or CTL attack, SET and NM23-H1 translocate to the nucleus and SET is degraded, allowing NM23-H1 to nick chromosomal DNA. GzmA-treated cells with silenced NM23-H1 expression are resistant to GzmA-mediated DNA damage and cytolysis, while cells overexpressing NM23-H1 are more sensitive.

    PMID: 12628186 [PubMed - indexed for MEDLINE]

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