Journal Article

FZJ-2013-05628

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Interaction of Bcl-2 with the autophagy-related GABAA receptor-associated protein (GABARAP): biophysical characterization and functional implications

ma, p.FZJ* ; Schwarten, M.FZJ* ; Schneider, L.FZJ* ; Boeske, A. ; Henke, N. ; Lisak, D. ; Weber, S.FZJ* ; Mohrluder, J.FZJ* ; Stoldt, M.FZJ* ; Strodel, B.FZJ* ; Methner, A. ; Hoffmann, S.FZJ* ; Weiergraber, O. H.FZJ* ; Willbold, D. (Corresponding author)FZJ*

2013
jbc Bethesda, Md.

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Please use a persistent id in citations: doi:10.1074/jbc.M113.528067

Abstract: Apoptosis 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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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 452 - Structural Biology (POF2-452) (POF2-452)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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