Linked Life Data

20064471

Source:http://linkedlifedata.com/resource/pubmed/id/20064471

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-1-12
pubmed:abstractText
The homeodomain protein TGIF functions as a negative regulator of multiple classes of transcription factors. Here we report on the characterization of TGIF as an essential component of the tumor necrosis factor alpha (TNF-alpha) cytotoxic program. This proapoptotic role of TGIF does not appear to rely on transcriptional modulation but instead is executed in conjunction with Itch/AIP4, an E3 ubiquitin ligase operating in TNF-alpha-induced apoptosis through its ability to target the caspase antagonist cFlip(L) for degradation. Notably, we found that activation of TNF-alpha signaling induced the association of TGIF with Itch/AIP4, resulting in increased accessibility of cFlip(L) for association and ubiquitination by Itch/AIP4. Moreover, we show that Itch/AIP4 can also stabilize the TGIF protein in response to TNF-alpha by triggering its monoubiquitination at lysine 259, thereby revealing the existence of a functional network that can evolve into a positive feedback loop for ensuring effective execution of the TNF-alpha apoptotic signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-4164
pubmed:author
pubmed:copyrightInfo
2009 Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1073-85
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A model of partnership co-opted by the homeodomain protein TGIF and the Itch/AIP4 ubiquitin ligase for effective execution of TNF-alpha cytotoxicity.
pubmed:affiliation
INSERM U, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't