Phosphorylation of Beclin 1 by DAP-kinase promotes autophagy by weakening its interactions with Bcl-2 and Bcl-XL

Autophagy. 2009 Jul;5(5):720-2. doi: 10.4161/auto.5.5.8625. Epub 2009 Jul 2.


Beclin 1, an essential autophagic protein, is a BH3-only protein that binds Bcl-2 anti-apoptotic family members. The dissociation of Beclin 1 from the Bcl-2 inhibitors is essential for its autophagic activity, and therefore is tightly controlled. We recently revealed a novel phosphorylation-based mechanism by which death-associated protein kinase (DAPk) regulates this process. We found that DAPk phosphorylates Beclin 1 on T119, a critical residue within its BH3 domain, and thus promotes Beclin 1 dissociation from Bcl-X(L) and autophagy induction. Here we report that T119 phosphorylation also reduces the interaction between Beclin 1 and Bcl-2, in line with the high degree of structural homology between the BH3 binding pockets of Bcl-2 and Bcl-X(L) proteins. Our results reveal a new phosphorylation-based mechanism that reduces the interaction of Beclin 1 with its inhibitors to activate the autophagic machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Death-Associated Protein Kinases
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Phosphorylation
  • Phosphothreonine / metabolism
  • Protein Binding
  • bcl-X Protein / metabolism*


  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • bcl-X Protein
  • Phosphothreonine
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases