Department of Biochemistry, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
Autophagy. 2011 Oct;7(10):1199-211. doi: 10.4161/auto.7.10.16649. Epub 2011 Oct 1.
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.
自噬在细胞分化和发育过程中的细胞重塑中起着重要作用，但关于其在干细胞中的调控知之甚少。在这里，我们表明，cAMP，一种众所周知的间充质干细胞（MSCs）分化因子，也是这些细胞中自噬的有效诱导剂。我们之前曾表明，尽管诱导了细胞周期成分细胞周期蛋白 E，但 cAMP 信号通路的激活会抑制 MSCs 的增殖。在这里，我们证明了细胞周期蛋白 E 在自噬诱导中的关键作用。我们的数据表明，cAMP 通过 ERK 介导的细胞周期蛋白 E 的诱导，导致 Beclin 1 向核周募集增加和自噬体的形成，这是一个模型。鉴于自噬失调在神经退行性疾病中的作用以及 cAMP 作为神经发生诱导物的作用，鉴定这种新的自噬途径可能为干预神经疾病提供新的靶点。
