HSpin1, a transmembrane protein interacting with BCl-2/Bcl-XL, induces a caspase-independent autophagic cell death

H. Yanagisawa, T. Miyashita, Y. Nakano, D. Yamamoto

    Research output: Contribution to journalArticlepeer-review

    86 Citations (Scopus)

    Abstract

    The Drosophila spinster (spin) gene product is required for programmed cell death in the nervous and reproductive systems. We have identified a human homologue of the Drosophila spin gene product (HSpin1). HSpin1 bound to Bcl-2 and apoptosis regulator Bcl-X (Bcl-XL), but not to proapoptotic members such as Bcl-2-associated X protein and Bcl-2 homologous antagonist killer, in cells treated with TNF-α. Exogenous expression of HSpin1 resulted in the cell death without inducing a release of cytochrome c from mitochondria. Overexpression of Bcl-XL inhibited the HSpin1-induced cell death. Interestingly, a necrosis inhibitor, pyrrolidine dithiocarbomate, but not the pancaspase inhibitors, carbobenzoxy-VAD-fluoromethyl ketone and p35, blocked the HSpin1-induced cell death. HSpin1-induced cell death increases autophagic vacuole and mature form of cathepsin D, suggesting a novel caspase-independent cell death, which is link to autophagy.

    Original languageEnglish
    Pages (from-to)798-807
    Number of pages10
    JournalCell Death and Differentiation
    Volume10
    Issue number7
    DOIs
    Publication statusPublished - 2003 Jul 1

    Keywords

    • Autophagic vacuoles
    • Bcl-2
    • Caspase-indenpendent cell death
    • Cathepsin D
    • Lipofuscin
    • Spinster

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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