Details

Autor(en) / Beteiligte

• Kao, C-J
• Chiang, Y-J
• Chen, P-H
• Lin, K-R
• Hwang, P-I
• Yang-Yen, H-F
• Yen, J J-Y

Titel

CBAP interacts with the un-liganded common β-subunit of the GM-CSF IL-3 IL-5 receptor and induces apoptosis via mitochondrial dysfunction

Ist Teil von

• Oncogene, 2008-02, Vol.27 (10), p.1397-1403

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2008

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The cytoplasmic domain of the common β-chain (βc) of the granulocyte–macrophage-colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptor contains a membrane proximal region that is sufficient to mediate ligand-dependent mitogenic activity. Within this region two motifs, designated as box 1 and box 2, are highly conserved among members of the cytokine receptor superfamily. Whereas box 1 is required for the recruitment and phosphorylation of Janus kinase-2, the function of box 2 remains largely unknown. Here, we report the identification of a novel transmembrane protein ( c ommon β-chain a ssociated p rotein (CBAP)) which directly associated with βc via the box 2 motif. Interestingly, such an association only occurred in the absence of GM-CSF in vivo . Ectopic overexpression of CBAP triggered apoptosis of factor-dependent cells via mitochondrial dysfunction, which could be inhibited by Bcl-2 overexpression. Reduced expression of endogenous CBAP by small interfering RNA did not interfere GM-CSF-activated signaling molecules, but such treatment significantly inhibited apoptosis induced by GM-CSF deprivation, but not other death stimuli. Domain mapping studies indicated that one apoptogenic domain of CBAP correlated with its ability to interact with βc. Taken together, these results suggest that CBAP modulates GM-CSF-deprivation-induced apoptosis possibly via a novel mechanism involving interaction with an un-liganded βc molecule.