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000139650 1001_ $$0P:(DE-Juel1)132033$$ama, peixiang$$b0$$ufzj
000139650 245__ $$aInteraction of Bcl-2 with the autophagy-related GABAA receptor-associated protein (GABARAP): biophysical characterization and functional implications
000139650 260__ $$aBethesda, Md.$$bjbc$$c2013
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000139650 520__ $$aApoptosis and autophagy are fundamental homeostatic processes in eukaryotic organisms fulfilling essential roles in development and adaptation. Recently, the anti-apoptotic factor Bcl-2 has been reported to also inhibit autophagy, thus establishing a potential link between these pathways, but the mechanistic details are only beginning to emerge. Here we show that Bcl-2 directly binds to the phagophore-associated protein GABARAP. NMR experiments revealed that the interaction critically depends on a three-residue segment (EWD) of Bcl-2 adjacent to the BH4 region, which is anchored to one of the two hydrophobic pockets on the GABARAP molecule. This is at variance with the majority of GABARAP interaction partners identified previously, which occupy both hydrophobic pockets simultaneously. Bcl-2 affinity could also be detected for GEC1, but not for other mammalian Atg8 homologs. Finally, we provide evidence that overexpression of Bcl-2 inhibits lipidation of GABARAP, a key step in autophagosome formation, possibly via competition with the lipid conjugation machinery. These results support the regulatory role of Bcl-2 in autophagy and define GABARAP as a novel interaction partner involved in this intricate connection.
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000139650 7001_ $$0P:(DE-Juel1)132019$$aSchwarten, M.$$b1
000139650 7001_ $$0P:(DE-Juel1)132785$$aSchneider, L.$$b2
000139650 7001_ $$0P:(DE-HGF)0$$aBoeske, A.$$b3
000139650 7001_ $$0P:(DE-HGF)0$$aHenke, N.$$b4
000139650 7001_ $$0P:(DE-HGF)0$$aLisak, D.$$b5
000139650 7001_ $$0P:(DE-Juel1)145819$$aWeber, Stephan$$b6
000139650 7001_ $$0P:(DE-Juel1)132012$$aMohrluder, J.$$b7
000139650 7001_ $$0P:(DE-Juel1)132023$$aStoldt, M.$$b8
000139650 7001_ $$0P:(DE-Juel1)132024$$aStrodel, B.$$b9
000139650 7001_ $$0P:(DE-HGF)0$$aMethner, A.$$b10
000139650 7001_ $$0P:(DE-Juel1)132003$$aHoffmann, Silke$$b11
000139650 7001_ $$0P:(DE-Juel1)131988$$aWeiergraber, O. H.$$b12
000139650 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b13$$eCorresponding author
000139650 773__ $$0PERI:(DE-600)1474604-9$$a10.1074/jbc.M113.528067$$gp. M113.528067$$p37204-37215$$tThe @journal of biological chemistry$$v288$$x1083-351X$$y2013
000139650 8564_ $$uhttp://www.jbc.org/content/early/2013/11/15/jbc.M113.528067.abstract#aff-1
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