TY  - JOUR
AU  - ma, peixiang
AU  - Schwarten, M.
AU  - Schneider, L.
AU  - Boeske, A.
AU  - Henke, N.
AU  - Lisak, D.
AU  - Weber, Stephan
AU  - Mohrluder, J.
AU  - Stoldt, M.
AU  - Strodel, B.
AU  - Methner, A.
AU  - Hoffmann, Silke
AU  - Weiergraber, O. H.
AU  - Willbold, Dieter
TI  - Interaction of Bcl-2 with the autophagy-related GABAA receptor-associated protein (GABARAP): biophysical characterization and functional implications
JO  - The journal of biological chemistry
VL  - 288
SN  - 1083-351X
CY  - Bethesda, Md.
PB  - jbc
M1  - FZJ-2013-05628
SP  - 37204-37215
PY  - 2013
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000329189700038
C6  - pmid:24240096
DO  - DOI:10.1074/jbc.M113.528067
UR  - https://juser.fz-juelich.de/record/139650
ER  -