Non-canonical function of Bax in stress-induced nuclear protein redistribution

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2013
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Lindenboim, Liora
Borner, Christoph
Stein, Reuven
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Cellular and Molecular Life Sciences. 2013, 70(16), pp. 3013-3027. ISSN 1420-682X. eISSN 1420-9071. Available under: doi: 10.1007/s00018-013-1306-4
Zusammenfassung

Bax and Bak (Bax/Bak) are essential pro-apoptotic proteins of the Bcl-2 family that trigger mitochondrial outer membrane permeabilization (MOMP) in a Bcl-2/Bcl-xL-inhibitable manner. We recently discovered a new stress-related function for Bax/Bak—regulation of nuclear protein redistribution (NPR) from the nucleus to cytoplasm. This effect was independent of Bax/Bak N-terminus exposure and not inhibited by Bcl-xL over-expression. Here, we studied the molecular mechanism governing this novel non-canonical response. Wild-type (WT) and mutant versions of Bax were re-expressed in Bax/Bak double-knockout mouse embryonic fibroblasts and their ability to promote NPR, apoptotic events, and changes in lamin A mobility was examined. Our results show that, in this system, Bax expression was sufficient to restore NPR such as in WT cells undergoing apoptosis. This activity of Bax was uncoupled from cytochrome c release from the mitochondria (indicative of MOMP) and required its membrane localization, α helices 5/6, and the Bcl-2 homology 3 (BH3) domain. Moreover, enrichment of Bax in the nuclear envelope by the so-called Klarsicht/ANC-1/Syne-1 homology domain effectively triggered NPR as in WT Bax, but without inducing MOMP or cell death. Bax-induced NPR was associated with impairment in lamin A mobility, implying a connection between these two nuclear envelope-associated events. Overall, the results indicate a new MOMP-independent, stress-induced Bax function on the nuclear envelope.

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570 Biowissenschaften, Biologie
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Apoptosis, Bcl-2 proteins, nucleus, nuclear permeability
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ISO 690LINDENBOIM, Liora, Elisa FERRANDO-MAY, Christoph BORNER, Reuven STEIN, 2013. Non-canonical function of Bax in stress-induced nuclear protein redistribution. In: Cellular and Molecular Life Sciences. 2013, 70(16), pp. 3013-3027. ISSN 1420-682X. eISSN 1420-9071. Available under: doi: 10.1007/s00018-013-1306-4
BibTex
@article{Lindenboim2013-08Nonca-23711,
  year={2013},
  doi={10.1007/s00018-013-1306-4},
  title={Non-canonical function of Bax in stress-induced nuclear protein redistribution},
  number={16},
  volume={70},
  issn={1420-682X},
  journal={Cellular and Molecular Life Sciences},
  pages={3013--3027},
  author={Lindenboim, Liora and Ferrando-May, Elisa and Borner, Christoph and Stein, Reuven}
}
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