title: cAMP induces autophagy via a novel pathway involving ERK, cyclin E and Beclin 1.
abstract: Autophagy plays an important role in cellular remodelling during differentiation and development, however little is known about its regulation in stem cells. Here we show that cAMP, a well-known differentiation factor for mesenchymal stem cells (MSCs), is also a potent inducer of autophagy in these cells. We have previously shown that activation of the cAMP-signaling pathway inhibits proliferation of MSCs despite induction of the cell cycle component cyclin E. Here, we demonstrate a critical role of cyclin E in the induction of autophagy. Our data suggest a model in which cAMP-signaling via ERK-mediated induction of cyclin E leads to enhanced perinuclear recruitment of Beclin 1 and formation of autophagosomes. Given the roles of deregulated autophagy in neurodegenerative disorders and cAMP as a neurogenic inducer, identification of this novel autophagocytic pathway may provide new targets for intervention against neurological disorders.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Ugland
authors.forename: Soheil
authors.initials: S
authors.lastname: Naderi
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
authors.forename: Heidi Kiil
authors.initials: HK
authors.lastname: Blomhoff
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D002454:Cell Differentiation; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D019927:Cyclin E; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases