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

Oncogene volume 27, pages 1397–1403 (2008)Cite this article

Abstract

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 (common β-chain associated protein (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.

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Acknowledgements

We thank Huan-Bin Wu, Chiuan-Cheng Lin, Ya-Ting Tsai and Pei-Yi Shau for technical assistance and Dr Hsiu-Ming Shih for providing the L40 yeast strain and the LexA expressing plasmid, pBTM116. This work was supported in part by an intramural fund from Academia Sinica and by Grants NSC-95-2320-B-001-050, NSC-93-2320-B-001-041, NSC-94-2320-B-001-007 from the National Science Council of Taiwan to JJ-Y Yen.

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Authors and Affiliations

  1. Institute of Molecular Medicine, National Taiwan University Medical School, Taipei, Taiwan

    C-J Kao & J J-Y Yen

  2. Institute of Biomedical Sciences, Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

    C-J Kao, Y-J Chiang, P-H Chen, K-R Lin & J J-Y Yen

  3. Bioinformatics Core Laboratory, Agricultural Biotechnology Research Center,

    P-I Hwang

  4. Academia Sinica, Taipei, Taiwan

    P-I Hwang

  5. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

    H-F Yang-Yen

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  1. C-J Kao
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Correspondence to J J-Y Yen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kao, CJ., Chiang, YJ., Chen, PH. et al. CBAP interacts with the un-liganded common β-subunit of the GM-CSF/IL-3/IL-5 receptor and induces apoptosis via mitochondrial dysfunction. Oncogene 27, 1397–1403 (2008). https://doi.org/10.1038/sj.onc.1210778

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