TY - JOUR
T1 - HSpin1, a transmembrane protein interacting with BCl-2/Bcl-XL, induces a caspase-independent autophagic cell death
AU - Yanagisawa, H.
AU - Miyashita, T.
AU - Nakano, Y.
AU - Yamamoto, D.
N1 - Funding Information:
We thank Takashi Sugiyama (Olympus Optical Co. Ltd) for help with the use of the fluorescence microscope and for the gift of HEK293 cells. We are grateful to Hiroyuki Iwahana (Jichi Medical School) for the gift of HeLa cells, and Masayuki Miura and John C Reed for pcDNA–p35 and pBcl-xL– Flag genes, respectively. We thank the members of the Yamamoto Laboratory for advice and discussion. This work was supported in part by Special Cooperation Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology to Daisuke Yamamoto and by Waseda University Grant No. 2002B-031 to DY and Grant No 2002A-905 to Kazue Usui-Aoki.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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.
AB - 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.
KW - Autophagic vacuoles
KW - Bcl-2
KW - Caspase-indenpendent cell death
KW - Cathepsin D
KW - Lipofuscin
KW - Spinster
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U2 - 10.1038/sj.cdd.4401246
DO - 10.1038/sj.cdd.4401246
M3 - Article
C2 - 12815463
AN - SCOPUS:0037818296
VL - 10
SP - 798
EP - 807
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 7
ER -