Bcl-2 proteins regulate ER membrane permeability to luminal proteins during ER stress-induced apoptosis.

Bcl-2 proteins regulate ER membrane permeability to luminal proteins during ER stress-induced apoptosis.
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DOI:
10.1038/cdd.2010.68
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发表时间:
2011-01
影响因子:
12.4
通讯作者:
--
中科院分区:
生物学1区
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--
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Endoplasmic reticulum (ER) stress-induced apoptosis may arise from multiple environmental and pharmacologic causes but the precise mechanism(s) involved are not completely known. Members of Bcl-2 protein family are important regulators of apoptosis. Here we report that, in a process dependent on the pro-apoptotic Bcl-2 members Bax and Bak, exogenously expressed fluorescent protein localized to the ER lumen is released into the cytosol in cells undergoing ER stress. Upon ER stress induction, endogenous ER luminal proteins are also released into the cytosol in a similar fashion accompanied by translocation and anchorage of Bax to the ER membrane. In addition, Bax and tBid mediate a global increase in ER membrane permeability to ER luminal proteins in vitro. Importantly, anti-apoptotic Bcl-XL antagonizes the effects of pro-apoptotic Bcl-2 proteins on ER membrane permeability. Consistent with Bax translocation to the ER membrane in whole apoptotic cells, there is also increased tight association of Bax with the ER membrane correlated with the increase in ER membrane permeability in vitro. Overall, these data suggest that the regulation of ER membrane permeability by Bcl-2 proteins could be an important molecular mechanism of ER stress-induced apoptosis.
DOI: 10.1083/jcb.93.1.97
发表时间: 1982-04
期刊: The Journal of cell biology
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