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Nix and Nip3 Form a Subfamily of Pro-apoptotic Mitochondrial Proteins
Open accessAbstract
We have identified Nix, a homolog of the E1B 19K/Bcl-2 binding and pro-apoptotic protein Nip3. Human and murine Nix have a 56 and 53% amino acid identity to human and murine Nip3, respectively. The carboxyl terminus of Nix, including a transmembrane domain, is highly homologous to Nip3 but it bears a longer and distinct asparagine/proline-rich N terminus. Human Nip3 maps to chromosome 14q11.2-q12, whereas Nix/BNip3L was found on 8q21. Nix encodes a 23. 8-kDa protein but it is expressed as a 48-kDa protein, suggesting that it homodimerizes similarly to Nip3. Following transfection, Nix protein undergoes progressive proteolysis to an 11-kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin. Nix colocalizes with the mitochondrial matrix protein HSP60, and removal of the putative transmembrane domain (TM) results in general cytoplasmic and nuclear expression. When transiently expressed, Nix and Nip3 but not TM deletion mutants rapidly activate apoptosis. Nix can overcome the suppressers Bcl-2 and Bcl-XL, although high levels of Bcl-XL expression will inhibit apoptosis. We propose that Nix and Nip3 form a new subfamily of pro-apoptotic mitochondrial proteins.
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Cites
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Cited by
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Green, D. R., Galluzzi, L., & Kroemer, G. (2011) · Science · doi:10.1126/science.1201940 · Cited by 1,245
Essential role for Nix in autophagic maturation of erythroid cells
Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M., & Wang, J. (2008) · Nature · doi:10.1038/nature07006 · Cited by 1,185
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Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032
Role of BNIP3 and NIX in cell death, autophagy, and mitophagy
Zhang, J., & Ney, P. A. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2009.16 · Cited by 1,021
Ding, W.-X., Ni, H.-M., Li, M., Liao, Y., Chen, X., Stolz, D. B., Dorn, G. W., & Yin, X.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.119537 · Cited by 551
Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover
Rikka, S., Quinsay, M. N., Thomas, R. L., Kubli, D. A., Zhang, X., Murphy, A. N., & Gustafsson, Å. B. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2010.146 · Cited by 277
BNip3 Regulates Mitochondrial Function and Lipid Metabolism in the Liver
Glick, D., Zhang, W., Beaton, M., Marsboom, G., Gruber, M., Simon, M. C., Hart, J., Dorn, G. W., Brady, M. J., & Macleod, K. F. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00167-12 · Cited by 251
Nix directly binds to GABARAP: A possible crosstalk between apoptosis and autophagy
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Metadata
- Authors
- Chen, G., Cizeau, J., Vande Velde, C., Park, J. H., Bozek, G., Bolton, J., Shi, L., Dubik, D., & Greenberg, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 274
- Issue
- 1
- Pages
- 7-10
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2005528779
- Cited by
- 310
- References
- 1
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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