Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection

Alhousseynou Sall, Huifang M. Zhang, Dexin Qiu, Zhongbin Liu, Ji Yuan, Zhen Liu, Travis Lim, Xin Ye, David Marchant, Bruce McManus, Decheng Yang

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Abstract

Our previous study reported that mouse BNIP-21 (mBNIP-21) induces apoptosis through a mitochondria-dependent pathway. To map the functional domains of mBNIP-21, we performed mutational analyses and demonstrated that the BNIP-2 and Cdc42GAP homology (BCH) domain is required for apoptosis induction by mBNIP-21 targeting the mitochondria and inducing cytochrome c release. This pro-apoptotic activity was enhanced by coxsackievirus infection. However, deletion of the Bcl-2 homology 3 (BH3)-like domain, a well-known cell 'death domain' in proapoptotic Bcl-2 family proteins, did not affect the activity of mBNIP-21. These data were further supported by transfection of a mouse Bax (mBax) mutant, whose BH3 was replaced by the mBNIP-21 BH3-like domain. This replacement significantly reduced the pro-apoptotic activity of mBax. We also found that the predicted calcium binding domain has no contribution to the mBNIP-21-induced apoptosis. Further mapping of the motifs of BCH domain demonstrated that deletion of the hydrophobic motif proximal to the C-terminal of the BCH significantly reduced its proapoptotic activity. These findings suggest that mBNIP-21, as a member of the BNIP subgroup of the Bcl-2-related proteins, functions without need of BH3 but its BCH domain is critical for its activity in inducing cell elongation, membrane protrusions and apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)599-614
Number of pages16
JournalCellular Microbiology
Volume12
Issue number5
DOIs
StatePublished - May 1 2010

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Coxsackievirus Infections
Apoptosis
Mitochondria
Cell Death
Cell Surface Extensions
Cytochromes c
Transfection
Proteins
Calcium

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection. / Sall, Alhousseynou; Zhang, Huifang M.; Qiu, Dexin; Liu, Zhongbin; Yuan, Ji; Liu, Zhen; Lim, Travis; Ye, Xin; Marchant, David; McManus, Bruce; Yang, Decheng.

In: Cellular Microbiology, Vol. 12, No. 5, 01.05.2010, p. 599-614.

Research output: Contribution to journalArticle

Sall, Alhousseynou ; Zhang, Huifang M. ; Qiu, Dexin ; Liu, Zhongbin ; Yuan, Ji ; Liu, Zhen ; Lim, Travis ; Ye, Xin ; Marchant, David ; McManus, Bruce ; Yang, Decheng. / Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection. In: Cellular Microbiology. 2010 ; Vol. 12, No. 5. pp. 599-614.
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abstract = "Our previous study reported that mouse BNIP-21 (mBNIP-21) induces apoptosis through a mitochondria-dependent pathway. To map the functional domains of mBNIP-21, we performed mutational analyses and demonstrated that the BNIP-2 and Cdc42GAP homology (BCH) domain is required for apoptosis induction by mBNIP-21 targeting the mitochondria and inducing cytochrome c release. This pro-apoptotic activity was enhanced by coxsackievirus infection. However, deletion of the Bcl-2 homology 3 (BH3)-like domain, a well-known cell 'death domain' in proapoptotic Bcl-2 family proteins, did not affect the activity of mBNIP-21. These data were further supported by transfection of a mouse Bax (mBax) mutant, whose BH3 was replaced by the mBNIP-21 BH3-like domain. This replacement significantly reduced the pro-apoptotic activity of mBax. We also found that the predicted calcium binding domain has no contribution to the mBNIP-21-induced apoptosis. Further mapping of the motifs of BCH domain demonstrated that deletion of the hydrophobic motif proximal to the C-terminal of the BCH significantly reduced its proapoptotic activity. These findings suggest that mBNIP-21, as a member of the BNIP subgroup of the Bcl-2-related proteins, functions without need of BH3 but its BCH domain is critical for its activity in inducing cell elongation, membrane protrusions and apoptotic cell death.",
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AU - Sall, Alhousseynou

AU - Zhang, Huifang M.

AU - Qiu, Dexin

AU - Liu, Zhongbin

AU - Yuan, Ji

AU - Liu, Zhen

AU - Lim, Travis

AU - Ye, Xin

AU - Marchant, David

AU - McManus, Bruce

AU - Yang, Decheng

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