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

doi:10.1038/sj.cdd.4401246

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

Cell Death Differ. 2003 Jul;10(7):798-807. doi: 10.1038/sj.cdd.4401246.

Authors

H Yanagisawa¹, T Miyashita, Y Nakano, D Yamamoto

Affiliation

¹ School of Human Sciences and Advanced Research Institute for Science and Engineering, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.

PMID: 12815463
DOI: 10.1038/sj.cdd.4401246

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-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / genetics*
Caspase Inhibitors
Caspases / metabolism
Cathepsin D / metabolism
Cell Cycle Proteins
Cell Death / genetics
Enzyme Inhibitors / pharmacology
HeLa Cells
Humans
Membrane Proteins / genetics
Membrane Proteins / isolation & purification
Membrane Proteins / metabolism*
Membrane Transport Proteins
Microtubule-Associated Proteins
Phosphoproteins
Protein Binding / physiology
Protein Structure, Tertiary / physiology
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Pyrrolidines / pharmacology
Thiocarbamates / pharmacology
Tumor Necrosis Factor-alpha / metabolism
Tumor Necrosis Factor-alpha / pharmacology
Vacuoles / drug effects
Vacuoles / metabolism
bcl-X Protein

Substances

BCL2L1 protein, human
Caspase Inhibitors
Cell Cycle Proteins
Enzyme Inhibitors
Membrane Proteins
Membrane Transport Proteins
Microtubule-Associated Proteins
Phosphoproteins
Proto-Oncogene Proteins c-bcl-2
Pyrrolidines
Thiocarbamates
Tumor Necrosis Factor-alpha
bcl-X Protein
spindlin
pyrrolidine dithiocarbamic acid
Caspases
Cathepsin D