Identification of a small molecule that induces ATG5-and-cathepsin-l-dependent cell death and modulates polyglutamine toxicity.

ABSTRACT: Non-apoptotic cell death mechanisms are largely uncharacterized despite their importance in physiology and disease [1]. Here we sought to systematically identify non-apoptotic cell death pathways in mammalian cells. We screened 69,612 compounds for those that induce non-canonical cell death by counter screening in the presence of inhibitors of apoptosis and necrosis. We further selected compounds that require active protein synthesis for inducing cell death. Using this tiered approach, we identified NID-1 (Novel Inducer of Death-1), a small molecule that induces an active, energy-dependent cell death in diverse mammalian cell lines. NID-1-induced death required components of the autophagic machinery, including ATG5, and the lysosomal hydrolase cathepsin L, but was distinct from classical m

SUBMITTER: Varma H 

PROVIDER: S-EPMC3700633 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature