title: JNK regulates FoxO-dependent autophagy in neurons.
abstract: The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Madhumita
authors.initials: M
authors.lastname: Das
authors.forename: Judith
authors.initials: J
authors.lastname: Reilly
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001343:Autophagy / Q000235:genetics* / Q000502:physiology; D000071186:Beclin-1; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C508686:BNip3 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C519509:Crtc1 protein, mouse; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases