Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1.

Beclin 1, a subunit of the class III phosphatidylinositol 3-kinase complex, is a tumour suppressor with a central role in endocytic trafficking, cytokinesis and the cross-regulation between autophagy and apoptosis. Interestingly, not only reduced expression but also overexpression of Beclin 1 is correlated with cancer development and metastasis. Thus it seems necessary for the cell to balance the protein levels of Beclin 1. In the present study we describe a regulatory link between Beclin 1 and the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). We establish Nedd4 as a novel binding partner of Beclin 1 and demonstrate that Nedd4 polyubiquitinates Beclin 1 with Lys11- and Lys63-linked chains. Importantly, Nedd4 expression controls the stability of Beclin 1, and depletion of the Beclin 1-interacting protein VPS34 causes Nedd4-mediated proteasomal degradation of Beclin 1 via Lys11-linked polyubiquitin chains. Beclin 1 is thus the first tumour suppressor reported to be controlled by Lys11-linked polyubiquitination.

Pubmed ID: 21936852


  • Platta HW
  • Abrahamsen H
  • Thoresen SB
  • Stenmark H


The Biochemical journal

Publication Data

January 1, 2012

Associated Grants


Mesh Terms

  • Apoptosis Regulatory Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • Endosomal Sorting Complexes Required for Transport
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Phosphatidylinositol 3-Kinases
  • Protein Stability
  • Proteolysis
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Ubiquitination