Linked Life Data

21300786

Source:http://linkedlifedata.com/resource/pubmed/id/21300786

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-3-25
pubmed:abstractText
Subtilase cytotoxin (SubAB) that selectively cleaves BiP/GRP78 triggers the unfolded protein response (UPR) and protects mice from endotoxic lethality and collagen arthritis. We found that pretreatment of cells with SubAB suppressed tumor necrosis alpha (TNF-?)-induced activation of NF-?B and NF-?B-dependent chemokine expression. To elucidate underlying mechanisms, the involvement of C/EBP and Akt, putative regulators of NF-?B, was investigated. Among members of the C/EBP family, SubAB preferentially induced C/EBP?. Overexpression of C/EBP? suppressed TNF-?-induced NF-?B activation, and knockdown of C/EBP? attenuated the suppressive effect of SubAB on NF-?B. We identified that the ATF6 branch of the UPR plays a crucial role in the induction of C/EBP?. In addition to this effect, SubAB depressed basal and TNF-?-induced phosphorylation of Akt via the UPR. It was mediated by the induction of ATF6 and consequent activation of mTOR that dephosphorylated Akt. Inhibition of Akt attenuated activation of NF-?B by TNF-?, suggesting that the mTOR-Akt pathway is another target for SubAB-initiated, UPR-mediated NF-?B suppression. These results elucidated that SubAB blunts activation of NF-?B through ATF6-dependent mechanisms, i.e., preferential induction of C/EBP? and mTOR-dependent dephosphorylation of Akt.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1710-8
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Selective abrogation of BiP/GRP78 blunts activation of NF-?B through the ATF6 branch of the UPR: involvement of C/EBP? and mTOR-dependent dephosphorylation of Akt.
pubmed:affiliation
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't