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Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis.

AlphaA- and alphaB-crystallins are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have recently demonstrated that alphaB-crystallin interacts with the procaspase-3 and partially processed procaspase-3 to repress caspase-3 activation. Here, we demonstrate that human alphaA- and alphaB-crystallins prevent staurosporine-induced apoptosis through interactions with members of the Bcl-2 family. Using GST pulldown assays and coimmunoprecipitations, we demonstrated that alpha-crystallins bind to Bax and Bcl-X(S) both in vitro and in vivo. Human alphaA- and alphaB-crystallins display similar affinity to both proapoptotic regulators, and so are true with their antiapoptotic ability tested in human lens epithelial cells, human retina pigment epithelial cells (ARPE-19) and rat embryonic myocardium cells (H9c2) under treatment of staurosporine, etoposide or sorbitol. Two prominent mutants, R116C in alphaA-crystallin and R120G, in alphaB-crystallin display much weaker affinity to Bax and Bcl-X(S). Through the interaction, alpha-crystallins prevent the translocation of Bax and Bcl-X(S) from cytosol into mitochondria during staurosporine-induced apoptosis. As a result, alpha-crystallins preserve the integrity of mitochondria, restrict release of cytochrome c, repress activation of caspase-3 and block degradation of PARP. Thus, our results demonstrate a novel antiapoptotic mechanism for alpha-crystallins.

Pubmed ID: 14752512 RIS Download

Mesh terms: Animals | Apoptosis | Caspases | Cells, Cultured | Cytochromes c | Cytosol | Epithelial Cells | Etoposide | Genes, bcl-2 | Humans | Mitochondria | Mutation | Myocytes, Cardiac | Protein Transport | Proto-Oncogene Proteins c-bcl-2 | Rats | Sorbitol | Staurosporine | alpha-Crystallin A Chain | alpha-Crystallin B Chain | bcl-2-Associated X Protein | bcl-X Protein

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Associated grants

  • Agency: NEI NIH HHS, Id: R29 EY011372
  • Agency: NEI NIH HHS, Id: EY11372

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