HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death.
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-alpha. 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.
Yanagisawa
H
H
School of Human Sciences and Advanced Research Institute for Science and Engineering, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.
Miyashita
T
T
Nakano
Y
Y
Yamamoto
D
D
D001343:Autophagy / Q000235:genetics*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; C104434:spindlin; C020972:pyrrolidine dithiocarbamic acid; D020169:Caspases; D002402:Cathepsin D