期刊
AUTOPHAGY
卷 7, 期 10, 页码 1199-1211出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.7.10.16649
关键词
cAMP; autophagy; cyclin E; ERK; mesenchymal stem cells
类别
资金
- Norwegian Cancer Society
- Norwegian Research Council
- Jahre Foundation
- Blix Family Foundation
- Rachel and Otto Kr. Bruun's legacy
- Novo Nordisk Research Foundation
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.
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