cAMP induces autophagy via a novel pathway involving ERK, cyclin E and Beclin 1

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Cell Differentiation
  • Cell Proliferation
  • Cyclic AMP / metabolism*
  • Cyclin E / metabolism*
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Membrane Proteins / metabolism*
  • Nervous System Diseases / metabolism
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Time Factors


  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Cyclin E
  • Membrane Proteins
  • RNA, Small Interfering
  • Cyclic AMP
  • Extracellular Signal-Regulated MAP Kinases