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SPIN1 played a critical role in necrotic cell death in cultured human cells. SPIN1 bound the antiapoptotic protein BCL2 and the apoptosis regulator BCLXL and induced cell death via a pathway that was independent of mitochondrial cytochrome c (CYCS) release and caspase activation. Mutation analysis showed that SPIN1 bound BCLXL via its BH3 domain. Necrosis inhibitors, but not caspase inhibitors, blocked SPIN1-induced cell death. SPIN1-induced cell death increased autophagic vacuole formation and the mature form of lysosomal cathepsin D (CTSD), suggesting SPIN1 induces necrotic cell death via autophagy.SPIN1 expression was also detected in HeLa and HEK293 cell lines. SPIN1 localized diffusely throughout the cytoplasm and concentrated in a punctate pattern that colocalized with a mitochondrial marker.
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