JAB1 accelerates mitochondrial apoptosis by interaction with proapoptotic BclGs.
The Bcl-2 family of proteins is the key regulators of cell apoptosis at the mitochondria level. The BH3-only pro-apoptotic member BclGs was unique among the family due to its highly specific expression in human testis and has been demonstrated to induce apoptosis dependent on the BH3 domain. However, the molecular mechanism of BclGs-induced apoptosis remains unclear. Here we show that overexpression of BclGs could induce Bax expression upregulation and translocation to mitochondria, cytochrome c release and activation of caspase-3. Moreover, we identified JAB1 as a novel BclGs-specific binding protein through a yeast two-hybrid screening in a human testis cDNA library. BclGs interacts with JAB1 both in vitro and in vivo. N-terminal region of BclGs (aa 1-67) was required for the interaction. Importantly, JAB1 and BclGs co-expression synergistically induces apoptosis. JAB1 could compete with Bcl-XL/Bcl-2 to bind to BclGs; thus, promote the apoptosis. RNAi-mediated knock-down of JAB1 results in the reduced proapoptotic activity of BclGs. Taken together, our results provided the first evidence that JAB1 is involved in the regulation of mitochondrial apoptotic pathway through specific interaction with BclGs.
Liu
Xiangjun
X
State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
Pan
Zhi
Z
Zhang
Lingqiang
L
Sun
Qiao
Q
Wan
Jinghong
J
Tian
Chunyan
C
Xing
Guichun
G
Yang
Juntao
J
Liu
Xiaolin
X
Jiang
Jizhi
J
He
Fuchu
F
D017209:Apoptosis / Q000502:physiology*; D000075686:COP9 Signalosome Complex; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494826:BAX protein, human; C494811:BCL2L1 protein, human; C428448:BCL2L14 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D053148:Caspase 3