Science · 2004 · 1.2K citations · 16 references
Life SciencesCell BiologyPathobiologyApoptosisAutophagySignal TransductionApoptosis ModulationApoptosis RegulationApoptotic SignalingCaspase ActivationProgrammed Cell DeathAutophagic Cell DeathC-jun N-terminal Kinase SignalingCaspase SignalingCell Death Signaling PathwaysJun N-terminal Kinase SignalingProgrammed Cell Death PathwaysProgrammed Cell Death RegulationReceptor Serine/threonine Kinase Signaling
Caspases are central to apoptosis, a well‑studied programmed cell‑death pathway, while other death programs such as necrosis and autophagy exist but their regulatory links to apoptosis remain unclear. The study defines a novel pathway where activation of receptor‑interacting protein kinase and JNK induces autophagy‑like cell death. The pathway is mediated by activation of receptor‑interacting protein kinase and Jun amino‑terminal kinase, driving autophagic‑morphology cell death. Autophagic death required ATG7 and beclin 1 and was triggered by caspase‑8 inhibition, indicating that caspase inhibitors used clinically may halt apoptosis yet inadvertently promote autophagic cell death.
Caspases play a central role in apoptosis, a well-studied pathway of programmed cell death. Other programs of death potentially involving necrosis and autophagy may exist, but their relation to apoptosis and mechanisms of regulation remains unclear. We define a new molecular pathway in which activation of the receptor-interacting protein (a serine-threonine kinase) and Jun amino-terminal kinase induced cell death with the morphology of autophagy. Autophagic death required the genes ATG7 and beclin 1 and was induced by caspase-8 inhibition. Clinical therapies involving caspase inhibitors may arrest apoptosis but also have the unanticipated effect of promoting autophagic cell death.
16
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Xiao Huan Liang, Saadiya Jackson, Matthew Seaman et al. · Nature · 1999 · 3.3K citations
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Xueping Qu, Jie Yu, Govind Bhagat et al. · Journal of Clinical Investigation · 2003 · 2.2K citations · Full text
Life Sciences, Genetics, Oncology +15