Lack of binding observed between human alpha-synuclein and Bcl-2 protein family.
alpha-Synuclein is a presynaptic protein of unknown function that has been implicated in the pathogenesis of Parkinson's disease. To gain insight into the function of alpha-synuclein, the present study examined the association between alpha-synuclein and the following Bcl-2 family proteins: Bcl-2; Bcl-XL; Bcl-associated death promoter (BAD); and Bcl-2-associated X-protein. The results of a binding assay using gluthathione S-transferase (GST) fusion alpha-synuclein protein and an immunoprecipitation assay revealed that wild-type or mutant (A30P and A53T) alpha-synuclein (approximately 16 kDa) does not bind to any of these members of the Bcl-2 family. Furthermore, no binding was observed between alpha-synuclein and BAD, regardless of the phosphorylation state of the serine residue in BAD. In contrast, alpha-synuclein was observed to bind to synphilin-1. Although alpha-synuclein has been reported to bind to BAD, modification of alpha-synuclein might be required for such binding to occur.
Nagano
Y
Y
Third Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan.
Yamashita
H
H
Nakamura
T
T
Takahashi
T
T
Kondo
E
E
Nakamura
S
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019556:COS Cells; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002352:Carrier Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051843:Synucleins; D016559:Tacrolimus / Q000494:pharmacology; D051844:alpha-Synuclein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D065095:Calcineurin Inhibitors; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051843:Synucleins; D051844:alpha-Synuclein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D019703:Calcineurin; D016559:Tacrolimus