Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy.
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.
Institut für Strukturbiologie und Biophysik, Forschungszentrum Jülich, Jülich, Germany.
Melanie
M
Schwarten
Jeannine
J
Mohrlüder
Peixiang
P
Ma
Matthias
M
Stoldt
Yvonne
Y
Thielmann
Thomas
T
Stangler
Nils
N
Hersch
Bernd
B
Hoffmann
Rudolf
R
Merkel
Dieter
D
Willbold
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013499:Surface Properties
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C505659:BNIP3L protein, rat; C116741:GABARAP protein, human; D008024:Ligands; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins