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Human Bop is a novel BH3-only member of the Bcl-2 protein family

Protein & Cell volume 3, pages 790–801 (2012)Cite this article

Abstract

One group of Bcl-2 protein family, which shares only the BH3 domain (BH3-only), is critically involved in the regulation of programmed cell death. Herein we demonstrated a novel human BH3-only protein (designated as Bop) which could induce apoptosis in a BH3 domain-dependent manner. Further analysis indicated that Bop mainly localized to mitochondria and used its BH3 domain to contact the loop regions of voltage dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane. In addition, purified Bop protein induced the loss of mitochondrial transmembrane potential (Δψm) and the release of cytochrome c. Furthermore, Bop used its BH3 domain to contact pro-survival Bcl-2 family members (Bcl-2, Bcl-XL, Mcl-1, A1 and Bcl-w), which could inhibit Bop-induced apoptosis. Bop would be constrained by pro-survival Bcl-2 proteins in resting cells, because Bop became released from phosphorylated Bcl-2 induced by microtubule-interfering agent like vincristine (VCR). Indeed, knockdown experiments indicated that Bop was partially required for VCR induced cell death. Finally, Bop might need to function through Bak and Bax, likely by releasing Bak from Bcl-XL sequestration. In conclusion, Bop may be a novel BH3-only factor that can engage with the regulatory network of Bcl-2 family members to process intrinsic apoptotic signaling.

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Affiliations

  1. The Key Laboratory of Infection and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Xiaoping Zhang, Changjiang Weng, Yuan Li, Xiaoyan Wang, Xuemei Li, Youli Xu, Lei Pan & Hong Tang

  2. National Key Laboratory of Bio-membrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China

    Chunsun Jiang & Quan Chen

  3. The Graduate School of Chinese Academy of Sciences, Beijing, 100049, China

    Xiaoping Zhang & Yuan Li

  4. Taizhou Institute of Protein Engineering, Taizhou National Biomedicine Hightech Park, Jiangsu, 225300, China

    Xiaoyan Wang

Authors
  1. Xiaoping Zhang
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  2. Changjiang Weng
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  3. Yuan Li
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  4. Xiaoyan Wang
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  5. Chunsun Jiang
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  6. Xuemei Li
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  7. Youli Xu
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  8. Quan Chen
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  9. Lei Pan
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  10. Hong Tang
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Corresponding authors

Correspondence to Lei Pan or Hong Tang.

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These authors contributed equally to the work.

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Zhang, X., Weng, C., Li, Y. et al. Human Bop is a novel BH3-only member of the Bcl-2 protein family. Protein Cell 3, 790–801 (2012). https://doi.org/10.1007/s13238-012-2069-7

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  • DOI: https://doi.org/10.1007/s13238-012-2069-7

Keywords

  • apoptosis
  • BH3 domain
  • Bop