Linked Life Data

21856935

Source:http://linkedlifedata.com/resource/pubmed/id/21856935

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-9-8
pubmed:abstractText
Fas ligand (FasL) belongs to the TNF family of death ligands, and its binding to the FasR leads to activation of several downstream signaling pathways and proteins, including NF-?B and PI3K/Akt. However, it is not known whether cross-talk exists between NF-?B and PI3K/Akt in the context of FasL signaling. We demonstrate using both human renal epithelial 293T cells and Jurkat T-lymphocyte cells that although FasL activates both Akt and NF-?B, Akt inhibits FasL-dependent NF-?B activity in a reactive oxygen species-dependent manner. Cellular FLICE-inhibitory protein (c-FLIP), an antioxidant and an important component of the death-inducing signaling complex, also represses NF-?B upstream of the regulatory I?B kinase-? protein subunit in the NF-?B signaling pathway, and positive cross-talk exists between Akt and c-FLIP in the context of inhibition of FasL-induced NF-?B activity. The presence of two death effector domains of c-FLIP and S-nitrosylation of its caspase-like domain were found to be important for mediating c-FLIP-dependent downregulation of NF-?B activity. Taken together, our study reveals a novel link between NF-?B and PI3K/Akt and establishes c-FLIP as an important regulator of FasL-mediated cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3256-66
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Antioxidant c-FLIP inhibits Fas ligand-induced NF-kappaB activation in a phosphatidylinositol 3-kinase/Akt-dependent manner.
pubmed:affiliation
Department of Pharmaceutical Sciences, Hampton University, Hampton, VA 23668, USA. anand.iyer@hamptonu.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural