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BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3
M Yasuda1, J W Han, C A Dionne
1Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110, USA.
Abstract:
Apoptosis is regulated by interaction of viral and cellular BCL-2 family antiapoptotic proteins with various pro-apoptotic proteins, several of which are also members of the BCL-2 family. Cellular protein BNIP3 is a BCL-2 family proapoptotic protein that interacts with viral antiapoptosis proteins such as adenoviruses E1B-19K and EBV-BHRF1 and cellular antiapoptosis proteins such as BCL-2 and BCL-xL. Database searches indicate that the human genome encodes an open reading frame for a protein, BNIP3alpha, that shares substantial homology with BNIP3. The BNIP3alpha open reading frame encodes a protein of 219 amino acids that contains a conserved BH3 domain and a COOH-terminal trans-membrane domain, characteristic of several BCL-2 family proapoptotic proteins. BNIP3alpha interacts with viral antiapoptosis protein E1B-19K and cellular antiapoptosis proteins BCL-2 and BCL-xL. Overexpression of BNIP3alpha in transfected cells results in apoptosis and suppresses the antiapoptosis activity of E1B-19K and BCL-xL. Like BNIP3, BNIP3alpha seems to be predominantly localized in mitochondria. These results suggest that BNIP3alpha is a structural and functional homologue of BNIP3. BNIP3 and BNIP3alpha seem to be the first examples of homologues among the various human proapoptotic proteins. Northern blot analysis reveals that BNIP3alpha is expressed ubiquitously in most human tissues. In contrast, BNIP3 is expressed well in several human tissues and less abundantly in certain tissues such as placenta and lung. These results suggest that although BNIP3 and BNIP3alpha may promote apoptosis simultaneously in most human tissues, BNIP3alpha may play a more universal role.
Insights
A newly discovered protein, BNIP3alpha, acts as a pro-apoptotic factor similar to BNIP3. This protein interacts with viral and cellular anti-apoptosis proteins, suggesting a universal role in regulating cell death across human tissues.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Apoptosis regulation involves interactions between viral/cellular anti-apoptotic and pro-apoptotic proteins, including BCL-2 family members.
- Cellular protein BNIP3, a BCL-2 family pro-apoptotic protein, interacts with viral and cellular anti-apoptosis proteins.
Purpose of the Study:
- To identify and characterize novel human pro-apoptotic proteins within the BCL-2 family.
- To investigate the functional and structural homology between BNIP3 and a newly identified protein, BNIP3alpha.
Main Methods:
- Database searches to identify the human genome's open reading frame for BNIP3alpha.
- Analysis of BNIP3alpha's protein structure, including conserved domains (BH3, transmembrane).
- Cell transfection studies to assess BNIP3alpha's effect on apoptosis and interaction with anti-apoptotic proteins (E1B-19K, BCL-2, BCL-xL).
- Subcellular localization studies (mitochondria).
- Northern blot analysis to determine BNIP3alpha tissue expression patterns.
Main Results:
- A human protein, BNIP3alpha, sharing homology with BNIP3, was identified.
- BNIP3alpha possesses a BH3 domain and transmembrane domain, characteristic of BCL-2 family pro-apoptotic proteins.
- BNIP3alpha interacts with viral (E1B-19K) and cellular (BCL-2, BCL-xL) anti-apoptotic proteins.
- Overexpression of BNIP3alpha induces apoptosis and counteracts the anti-apoptotic effects of E1B-19K and BCL-xL.
- BNIP3alpha, like BNIP3, localizes to mitochondria.
- BNIP3alpha is ubiquitously expressed in human tissues, unlike BNIP3 which shows variable expression.
Conclusions:
- BNIP3alpha is a structural and functional homologue of BNIP3, representing new examples of homology among human pro-apoptotic proteins.
- BNIP3alpha may play a more universal role in promoting apoptosis across human tissues compared to BNIP3.