Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy

Autophagy. 2009 Jul;5(5):690-8. doi: 10.4161/auto.5.5.8494. Epub 2009 Jul 20.

Abstract

Autophagy, a pathway primarily relevant for cell survival, and apoptosis, a process invariably leading to cell death, are the two main mechanisms of cellular self-destruction, which are essential in cell growth, neurodegeneration, tumor suppression, stress and immune response. Currently, a potential crosstalk between apoptosis and autophagy is subject to intensive investigations since recently some direct junctions became obvious. The respective protein-protein interaction network, however, remains to be elucidated in detail. The gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein GABARAP belongs to a family of proteins implicated in intracellular transport events and was shown to be associated to autophagic processes. Using a phage display screening against the target protein GABARAP, we identified the proapoptotic protein Nix/Bnip3L to be a potential GABARAP ligand. In vitro binding studies, pull-down analysis, coimmunoprecipitation assays and colocalization studies confirmed a direct interaction of both proteins in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Autophagy*
  • Humans
  • Immunoprecipitation
  • Jurkat Cells
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Protein Transport
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Surface Properties

Substances

  • Adaptor Proteins, Signal Transducing
  • BNIP3L protein, rat
  • GABARAP protein, human
  • Ligands
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mutant Proteins
  • Peptides
  • Proto-Oncogene Proteins