Abstract：
:Physiological oxidants that are generated by activated phagocytes comprise the main source of oxidative stress during inflammation. Oxidants such as taurine chloramine (TnCl) and hydrogen peroxide (H(2)O(2)) can damage proteins and induce apoptosis, but the role of specific protein oxidation in this process has not been defined. We found that the actin-binding protein cofilin is a key target of oxidation. When oxidation of this single regulatory protein is prevented, oxidant-induced apoptosis is inhibited. Oxidation of cofilin causes it to lose its affinity for actin and to translocate to the mitochondria, where it induces swelling and cytochrome c release by mediating opening of the permeability transition pore (PTP). This occurs independently of Bax activation and requires both oxidation of cofilin Cys residues and dephosphorylation at Ser 3. Knockdown of endogenous cofilin using targeted siRNA inhibits oxidant-induced apoptosis, which is restored by re-expression of wild-type cofilin but not by cofilin containing Cys to Ala mutations. Exposure of cofilin to TnCl results in intramolecular disulphide bonding and oxidation of Met residues to Met sulphoxide, but only Cys oxidation causes cofilin to induce mitochondrial damage.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Klamt F,Zdanov S,Levine RL,Pariser A,Zhang Y,Zhang B,Yu LR,Veenstra TD,Shacter Edoi
10.1038/ncb1968subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1241-6issue
10eissn
1465-7392issn
1476-4679pii
ncb1968journal_volume
11pub_type
杂志文章abstract：:Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms. Here, we report the identification of GEMC1 (geminin coiled-coil containing protein 1), a novel vertebrate protein required for chromoso...
journal_title：Nature cell biology
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更新日期：2010-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2001-07-01 00:00:00
abstract：:Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates embryonic development and tissue homeostasis; however, aberrations of its activity occur in cancer. TGF-beta signals through its Type II and Type I receptors (TbetaRII and TbetaRI) causing phosphorylation of Smad proteins. TGF-beta...
journal_title：Nature cell biology
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更新日期：2008-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2011-06-19 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1447
更新日期：2006-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3488
更新日期：2017-04-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1602
更新日期：2007-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncb1803
更新日期：2008-12-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1156
更新日期：2004-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb0509-510
更新日期：2009-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3575
更新日期：2017-09-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1102
更新日期：2004-03-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2151
更新日期：2011-02-01 00:00:00
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journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb1008-1131
更新日期：2008-10-01 00:00:00
abstract：:Compartmentalization has long been known to have a key role in regulation of cellular processes. By keeping enzymes and regulatory complexes in compartments where the delivery of substrate or exit of product is controlled, competing reactions can occur simultaneously in different parts of the cell. Moreover, spatial c...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/35014078
更新日期：2000-06-01 00:00:00
abstract：:The SNF2h (sucrose non-fermenting protein 2 homologue)-containing chromatin-remodelling complex NoRC silences a fraction of ribosomal RNA genes (rDNA) by establishing a heterochromatic structure at the rDNA promoter. Here we show that the acetyltransferase MOF (males absent on the first) acetylates TIP5, the largest s...
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pub_type： 杂志文章
doi：10.1038/ncb1914
更新日期：2009-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2017-09-29 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncb1568
更新日期：2007-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1188
更新日期：2004-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-03-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章,评审
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更新日期：2011-10-03 00:00:00
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更新日期：2003-04-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2010-09-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章,评审
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更新日期：2013-06-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1828
更新日期：2009-02-01 00:00:00
abstract：:Although it is well recognized that haematopoietic stem cells (HSCs) develop from a specialized population of endothelial cells known as haemogenic endothelium, the regulatory pathways that control this transition are not well defined. Here we identify Sox17 as a key regulator of haemogenic endothelial development. An...
journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2013-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1061
更新日期：2003-11-01 00:00:00
