Human αA- and αB-crystallins bind to Bax and Bcl-Xs to sequester their translocation during staurosporine-induced apoptosis

Y. W. Mao, J. P. Liu, H. Xiang, D. W.C. Li

Research output: Contribution to journalReview article

274 Citations (Scopus)

Abstract

αA- and αB-crystallins are distinct antiapoptotic regulators. Regarding the antiapoptotic mechanisms, we have recently demonstrated that αB-crystallin interacts with the procaspase-3 and partially processed procaspase-3 to repress caspase-3 activation. Here, we demonstrate that human αA- and αB-crystallins prevent staurosporine-induced apoptosis through interactions with members of the Bcl-2 family. Using GST pulldown assays and coimmunoprecipitations, we demonstrated that α-crystallins bind to Bax and Bcl-XS both in vitro and in vivo. Human αA- and αB-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 αA-crystallin and R120G, in αB-crystallin display much weaker affinity to Bax and Bcl-XS. Through the interaction, α-crystallins prevent the translocation of Bax and Bcl-XS from cytosol into mitochondria during staurosporine-induced apoptosis. As a result, α -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 α-crystallins.

Original languageEnglish (US)
Pages (from-to)512-526
Number of pages15
JournalCell Death and Differentiation
Volume11
Issue number5
DOIs
StatePublished - May 1 2004

Fingerprint

Crystallins
Staurosporine
Apoptosis
Caspase 3
Mitochondria
Epithelial Cells
Sorbitol
Etoposide
Cytochromes c
Cytosol
Lenses
Retina
Myocardium

Keywords

  • Bax
  • Bcl-X
  • R116C
  • R120G
  • αA-crystallin
  • αB-crystallin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Human αA- and αB-crystallins bind to Bax and Bcl-Xs to sequester their translocation during staurosporine-induced apoptosis. / Mao, Y. W.; Liu, J. P.; Xiang, H.; Li, D. W.C.

In: Cell Death and Differentiation, Vol. 11, No. 5, 01.05.2004, p. 512-526.

Research output: Contribution to journalReview article

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